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Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87–4098 and Duro-Tak@ 87–2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Intranasal drug delivery is as a noninvasive and efficient approach extensively utilized for treating the local, central nervous system, and systemic diseases. Despite numerous reviews delving into the application of intranasal drug delivery across biomedical fields, a comprehensive analysis of advancements and future perspectives remains elusive. This review elucidates the research progress of intranasal drug delivery through a scientometric analysis. It scrutinizes several challenges to bolster research in this domain, encompassing a thorough exploration of entry and elimination mechanisms specific to intranasal delivery, the identification of drugs compatible with the nasal cavity, the selection of dosage forms to surmount limited drug-loading capacity and poor solubility, and the identification of diseases amenable to the intranasal delivery strategy. Overall, this review furnishes a perspective aimed at galvanizing future research and development concerning intranasal drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

In this present research attempt has been made to enhance the solubility and dissolution of poorly soluble telmisartan by solid dispersion technique using pluronic F127 and implementation of multiple comparison analysis to screen the drug-carrier ratio to optimize the solubility and dissolution. All the solid dispersions were prepared by using various concentrations of drug and carrier and subjected to melting point, solubility and dissolution studies to optimize the drug-carrier ratio. Optimized solid dispersion was also subjected to various analytical studies such as field emission scanning electron microscope, differential scanning calorimetry, X-ray diffraction studies along with stability studies to identify the physico-chemical state of the prepared solid dispersion. It was observed from this research that prepared solid dispersions could able to improve the solubility and dissolution of telmisartan by 6.93 folds and 2.57 folds respectively. Statistical analysis revealed significant difference between telmisartan and prepared telmisartan-pluronic F127 solid dispersion with respect to their solubility and dissolution data. Field emission scanning electron microscope study revealed that distinctive crystalline structure and geometric shape of pure telmisartan was completely disappeared in the prepared solid dispersion which revealed the conversion of crystalline telmisartan to its amorphous form. Differential scanning calorimetry and X-ray diffraction studies confirmed the complete amorphization of drug crystals upon treating with pluronic F127. Stability study also confirmed the stable nature of the prepared telmisartan-pluronic F127 solid dispersion with shelf life of 1.62 y. Finally, it was concluded from the above experimental results that optimized concentration of pluronic F127 could able to improve the solubility and dissolution of telmisartan by solid dispersion technique. [ABSTRACT FROM AUTHOR]

The study was performed with a dual approach to develop and validate analytical method for poorly water soluble candesartan cilexetil by enhancing its solubility employing cosolvency technique. In order to enhance drug's solubility based on its solubility characteristics, phosphate buffer (pH 6.8):ethanol (95 % v/v) mixture at 90:10 proportion was used along with Tween 80 (1 % v/v). Solubility of candesartan cilexetil in phosphate buffer (pH 6.8) enhanced due to the addition of cosolvent ethanol and Tween 80. Developed method obeyed Beer-Lambert's law in the concentration range between 3-21 µg/ml. The regression coefficient at the wavelength 232 nm was 0.999. The analysis of tablets by the proposed method indicated a good correlation between estimated and labelled claims. Recovery studies showed that any small difference in drug concentration could be accurately determined. Low values of limit of detection and limit of quantitation indicated that the proposed method is sensitive, economic, accurate, precise, and robust for routine analysis of candesartan cilexetil in bulk and dosage forms. [ABSTRACT FROM AUTHOR]

Over the years, infectious diseases have significantly contributed to the mortality and morbidity rates in the healthcare system. Conventional treatments have been used for many years to treat infectious diseases, such as oral and topical drug delivery routes. However, these treatments present numerous challenges. The factors such as the solubility of the drug, its size and its molecular weight may affect the efficacy of conventional therapies. Nanotechnology or nanomedicine is one of the novel and promising approaches to overcome these aforementioned challenges for traditional therapies. Solid lipid nanoparticles are a novel approach in the drug delivery system which was first introduced in early 1990s. Their small size, large surface area, high drug loading and the ability to interact with other phases, solid lipid nanoparticles are attractive for improving the performance of pharmaceutical, nutraceutical and other materials. Solid lipid nanoparticles have been proven to be one of the most effective methods of treating infectious diseases (antibiotic-loaded solid lipid nanoparticles). This review emphasizes solid lipid nanoparticles as a delivery system for infectious diseases. Also, it discusses research pertaining to the targeting approach of solid lipid nanoparticles in infections. [ABSTRACT FROM AUTHOR]

Nanosponge can be considered as an effective carrier among all the novel drug delivery systems based on nanotechnology. It is a newer class of nanoparticulate system having 3-dimensional scaffold structure and nanometric cavity size. Owing to the highly porous nature, nanosponge can offer several benefits like capability to entrap multiple active moieties, loading both hydrophobic and hydrophilic drugs, enhancing the drug solubility followed by promoting the bioavailability of drug molecules, and exhibiting programmable release. These spherical shaped colloidal nanocarriers have the potential to elevate the solubility for poorly soluble drugs through their inclusion and non-inclusion activities. The drugs belonging to Biopharmaceutical Classification System class II and IV are the suitable candidates to be developed as nanosponge formulation for increasing their solubility. Emulsion solvent diffusion method, ultrasound-assisted synthesis, high pressure homogenization etc. are the popular methods for preparation of nanosponge. An extensive variety of additives such as polymers, copolymers, cross-linkers, surfactants are used for releasing the drugs to the target site in a predictable manner through various routes of administration like oral, parenteral, topical. In this review, an overview of nanosponge and its recent advancement in field of drug delivery system along with fu ture perspectives will be discussed. [ABSTRACT FROM AUTHOR]

Antibiotics are playing crucial role in the treatment of humans since the last few centuries. Their usage has several benefits along with side effects. The efficacy of antibiotics for the treatment of ailments may be retained by controlling the drug dosage. This may be achieved with supercritical fluid technology (SFT). The antibiotic drug solubility in supercritical carbon dioxide (scCO2) is available only at specific temperature and pressure conditions, for effective utilization of SFT, solubility at various conditions are required. Equation of state (EoS) method is used for solubility data modeling and it requires critical properties of the solute, molar volume of the solute and sublimation pressure of the solute along with fugacity coefficient, pressure and temperature. These properties are estimated using group contribution methods. For antibiotics solute critical properties, molar volume and sublimation pressure are unavailable and existing group contribution methods are also not applicable due to the lack of functional group contributions in their techniques. Thus, there is a need to address EoS methodology without using solute properties. Hence, a new EoS methodology for solubility modeling is, proposed without using critical properties of the solute, molar volume of the solute and vapour pressure of the solute. Thus, this study focuses on the development of new solubility model that correlates antibiotics using equation of state (EoS). Importantly, the proposed solubility model does not use the critical properties of the antibiotics. Correlating ability of the proposed model is indicated in terms of regression coefficient and arithmetic average relative deviation percentage (AARD %). [ABSTRACT FROM AUTHOR]

The study and characterization of the biophysical properties of membranes and drug–membrane interactions represent a critical step in drug development, as biological membranes act as a barrier that the drug must overcome to reach its active site. Liposomes are widely used in drug delivery to circumvent the poor aqueous solubility of most drugs, improving systemic bioavailability and pharmacokinetics. Further, they can be targeted to deliver to specific disease sites, thus decreasing drug load, and reducing side effects and poor adherence to treatment. To improve drug solubility during liposome preparation, DMSO is the most widely used solvent. This raises concern about the potential effect of DMSO on membranes and leads us to investigate, using DSC and EPR, the influence of DMSO on the behavior of lipid model membranes of DMPC and DPPC. In addition, we tested the influence of DMSO on drug–membrane interaction, using compounds with different hydrophobicity and varying DMSO content, using the same experimental techniques. Overall, it was found that with up to 10% DMSO, changes in the bilayer fluidity or the thermotropic properties of the studied liposomes were not significant, within the experimental uncertainty. For higher concentrations of DMSO, there is a stabilization of both the gel and the rippled gel phases, and increased bilayer fluidity of DMPC and DPPC liposomes leading to an increase in membrane permeability. [ABSTRACT FROM AUTHOR]

Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%. [ABSTRACT FROM AUTHOR]

To investigate the in-situ physicochemical interaction of Rifampicin and Ritonavir - Lopinavir Solid dispersion administered for the treatment of comorbid conditions i.e. Tuberculosis and HIV/AIDS. pH-shift dissolution of Rifampicin (RIF) in presence of Ritonavir-Lopinavir solid dispersion (RL-SD) was carried out in USP phosphate buffer 6.8 and FaSSIF. Equilibrium and amorphous solubility were determined for the drugs. Pure drugs, their physical mixtures, and pH-shifted co-precipitated samples were characterized using DSC, PXRD, and FTIR. Fluorescence spectroscopy was used to investigate drug-rich and drug-lean phases. In-vitro and ex-vivo flux studies were also carried out. The results showed significant differences in the solubility and dissolution profiles of RTV and LOP in the presence of RIF, while RIF profile remained unchanged. Amorphicity, intermolecular interaction and aggregate formation in pH-shifted samples were revealed in DSC, XRD and FTIR analysis. Fluorescence spectroscopy confirmed the formation of drug-rich phase upon pH-shift. In-vitro and ex-vivo flux studies revealed significant reduction in the flux of all the drugs when studied in presence of second drug. RIF, RTV and LOP in presence of each other on pH-shift, results in co-precipitation in the amorphous form (miscible) which leads to reduction in the highest attainable degree of supersaturation. This reduction corresponds to the mole fraction of the RIF, RTV and LOP within the studied system. These findings suggest that the concomitant administration of these drugs may lead to physicochemical interactions and possible ineffective therapy. [ABSTRACT FROM AUTHOR]

The design of new drug delivery systems has been widely sought after. The stability, solubility, and difficulty of targeting active sites for new drugs have always been challenging and remain one of the major drawbacks to the efficiency of certain drugs. Liposomes are phospholipid vesicles enclosing one or more aqueous compartments. Depending on its properties, a drug is embedded in the lipid bilayer or the aqueous medium. Thus, liposomes can act as drug carriers for both lipo- and hydrophilic compounds. New strategies such as "drug-in-cyclodextrin-in liposomes" (DCLs) have been developed as safe and effective carriers for exploiting the inclusion properties of water-soluble cyclodextrins known to form host–guest complexes with lipophilic molecules. Once inclusion complexes are formed, they can be inserted into a liposome aqueous core in order to stabilize it and better control the drug release. Our review will provide an update on the use of DCLs in the field of drug delivery for various kinds of active compounds. While previous reviews focused on the interesting advantages of using this method, such as enhancing the solubility and stability of a drug or controlling and improving drug release, the authors intend to highlight the impact of these nanocarriers on the pharmacokinetic and/or pharmacodynamic properties of drugs. [ABSTRACT FROM AUTHOR]

This document is an editorial for a special issue of the journal Pharmaceutics on the topic of the pharmacokinetics of orally administered drugs. The editorial highlights the importance of oral drug administration and the challenges that limit the bioavailability of orally administered drugs. The special issue contains six original articles that discuss various approaches to improve the bioavailability and pharmacokinetic profile of orally administered drugs, including the development of new formulations and the use of nanoformulations. The editorial concludes by stating that the papers presented in the special issue are of interest to the scientific community and can guide the application of new oral formulations in clinical practice. [Extracted from the article]

Biological variability poses significant challenges in the development of effective therapeutics, particularly when it comes to drug solubility and bioavailability. Poor solubility across varying physiological conditions often leads to reduced absorption and inconsistent therapeutic outcomes. This review examines how nanotechnology, especially through the use of nanomaterials and magnetic nanoparticles, offers innovative solutions to enhance drug solubility and bioavailability. This comprehensive review focuses on recent advancements and approaches in nanotechnology. We highlight both the successes and remaining challenges in this field, emphasizing the role of continued innovation. Future research should prioritize developing universal therapeutic solutions, conducting interdisciplinary research, and leveraging personalized nanomedicine to address biological variability.

In this work, an extension of the Madrid-2019 force field is presented. We have added the cations Rb+ and Cs+ and the anions F−, Br−, and I−. These ions were the remaining alkaline and halogen ions, not previously considered in the Madrid-2019 force field. The force field, denoted as Madrid-2019-Extended, does not include polarizability and uses the TIP4P/2005 model of water and scaled charges for the ions. A charge of ±0.85e is assigned to monovalent ions. The force field developed provides an accurate description of aqueous solution densities over a wide range of concentrations up to the solubility limit of each salt studied. Good predictions of viscosity and diffusion coefficients are obtained for concentrations below 2 m. Structural properties obtained with this force field are also in reasonable agreement with the experiment. The number of contact ion pairs has been controlled to be low so as to avoid precipitation of the system at concentrations close to the experimental solubility limit. A comprehensive comparison of the performance for aqueous solutions of alkaline halides of force fields of electrolytes using scaled and integer charges is now possible. This comparison will help in the future to learn about the benefits and limitations of the use of scaled charges to describe electrolyte solutions. [ABSTRACT FROM AUTHOR]

In this work, an extension of the Madrid-2019 force field is presented. We have added the cations Rb+ and Cs+ and the anions F−, Br−, and I−. These ions were the remaining alkaline and halogen ions, not previously considered in the Madrid-2019 force field. The force field, denoted as Madrid-2019-Extended, does not include polarizability and uses the TIP4P/2005 model of water and scaled charges for the ions. A charge of ±0.85e is assigned to monovalent ions. The force field developed provides an accurate description of aqueous solution densities over a wide range of concentrations up to the solubility limit of each salt studied. Good predictions of viscosity and diffusion coefficients are obtained for concentrations below 2 m. Structural properties obtained with this force field are also in reasonable agreement with the experiment. The number of contact ion pairs has been controlled to be low so as to avoid precipitation of the system at concentrations close to the experimental solubility limit. A comprehensive comparison of the performance for aqueous solutions of alkaline halides of force fields of electrolytes using scaled and integer charges is now possible. This comparison will help in the future to learn about the benefits and limitations of the use of scaled charges to describe electrolyte solutions. [ABSTRACT FROM AUTHOR]

Glipizide, a poor water-soluble drug belongs to BCS class II. The proposed work aimed to enhance the solubility of glipizide by preparing solid dispersions, using polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). Solvent evaporation method was used for the preparation of glipizide solid dispersions. Solid dispersions were prepared in four different drug-to-polymer ratios i.e. 1:1, 1:2, 1:3 and 1:4. Mainly effect of three polymers (PVP K30, PVP K90 and PEG 6000) was evaluated on the solubility and dissolution of glipizide. The in-vitro dissolution of all prepared formulations was performed under pH 6.8 at 37°C using USP type II apparatus. In-vitro dissolution results revealed that the formulations having high concentrations of the polymer showed enhanced solubility. Enhancements in the solubility and rate of dissolution of the drug were noted in solid dispersion formulations compared to the physical blends and pure drug. Solid dispersions containing polyvinyl pyrrolidone exhibited a more favorable pattern of drug release compared to the corresponding solid dispersions with PEG. An increase in the maximum solubility of the drug within the solid dispersion systems was observed in all instances. Two solid dispersion formulations were optimized and formulated into immediate-release tablets, which passed all the pharmacopoeial and non-pharmacopoeial tests. Fourier transformed Infrared (FTIR) spectroscopy X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) were used to indicate drug: polymer interactions in solid state. Analysis of the solid dispersion samples through characterization tests indicated the compatibility between the drug and the polymer. [ABSTRACT FROM AUTHOR]

The drug–drug multicomponent crystals (cocrystal/salt) in pharmaceutical products may boost the major challenges of fixed-dose combinations (FDCs) in coming years. The challenges associated with FDCs such as drug incompatibility, solubility differences, and stability issues can be overcome by salt/cocrystallization. Herein, the authors report eight drug–drug/drug–nutraceutical salts of the anti-emetic drug domperidone (DOM) with various drug coformers such as nicotinic acid (NCA), DL -mandelic acid (MAA), salicylic acid (SLA), orotic acid (OTA), and aspirin (ASP). The single-crystal X-ray diffraction study revealed multiple solid forms in DOM–NCA and DOM–MAA salts which differ by the presence of water. The salts, namely, DOM–MAA, DOM–OTA and DOM–ASP crystallized as anhydrous salts. The salts DOM–NCA I, DOM–SLA, and DOM–MAA I were found to be similar in crystal packing based on CrystalCMP software. The prepared salts showed lower melting temperatures as compared to DOM and coformers except for DOM–OTA. The solubility of the prepared salts in three different buffer media revealed enhancement in the solubility of DOM in pH 6.8 and 1.2 buffers. The solubility of DOM in the salts was drastically reduced in the acetate buffer (pH 4.6) as compared to the parent DOM. The dissolution study in pH 6.8 buffer demonstrated the faster drug release in the salts. The prepared salts exhibited stability under accelerated humidity conditions (40 °C, 70–75% RH) for 30 days, demonstrating the possibility of further developing these drug–drug/drug–nutraceutical salts. [ABSTRACT FROM AUTHOR]

5-Fluorouracil is a chemotherapeutic agent used for the treatment of different kinds of cancers and Amlodipine Besylate is a vasodilator used to cure hypertension and angina. In order to improve different properties of drugs like drug solubility, mask bitter taste, prevent photodegradation, and for controlled drug delivery, the host–guest, solid inclusion complexes of 5-flurouracil (5-FU) and Amlodipine Besylate (ABS) with beta-cyclodextrin (β-CD) were utilized for different studies in this manuscript which were prepared through traditional methods and microwave-prompted technique. Different parameters such as apparent molar volume (Vϕ), partial molar volume at infinite dilution (Vϕ0), apparent molar isentropic compression (Kϕ,s), partial molar isentropic compression at infinite dilution (K0ϕ,s) were obtained from experimental density and speed of sound data. The partial molar volume at infinite dilution (Vϕ0 × 106/m3 mol−1) values of β-CD in aqueous solution of drug ABS was found 79.83, 80.32 and 80.64 at 305.15, 310.15 and 315.15 K, respectively. The partial molar volume at infinite dilution (Vϕ0 × 106/m3 mol−1) values of β-CD in aqueous solution of drug 5-FU was found − 252.61, − 246.42 and − 255.74 at 305.15, 310.15 and 315.15 K, respectively. The value of solubility constant (Ks) was found to be 74.3822 ± 4 M−1 for 5-FU and 204.0811 ± 4.75 M−1 for ABS in phase solubility studies. The inclusion complexes (ICs) were incorporated into the hybrid polymer networks (HPNs) of chitosan and gelatin to explore drug release studies. A comparison of directly loaded drug into the HPNs was made with the cyclodextrin-mediated release. The ICs prepared by different methods were also compared for the drug release. [ABSTRACT FROM AUTHOR]

Raltegravir (RLT) is a human immunodeficiency virus integrase strand transfer inhibitor that is prescribed for the treatment of HIV-1 infection. The drug belongs to biopharmaceutics classification system (BCS) class II category and has poor aqueous solubility and chemical stability in acidic/basic medium. Polymorph screening was performed to search for an alternative solid form with improved drug attributes. By serendipity, this screening gave anhydrous RLT (form A) and two crystalline solid phases of impurity C. The RLT form A and impurity C were characterised using powder X-ray diffraction (XRD), thermal analysis (differential scanning calorimetry/thermogravimetric analysis) and vibrational spectroscopy (Fourier-transform infrared). The crystal structures of form A and impurity C were determined from the high resolution powder XRD patterns using Rietveld refinement, thus revealing their conformational and synthon differences. The crystal structure of impurity C1 (MeOH solvate) was solved from single crystal XRD and demonstrates the packing and conformational differences compared to parent phase C. The dissolution/solubility experiments confirmed that form A has a higher solubility than its hydrate in aqueous ethanol medium. Compared to the commercialized RLT potassium salt (RLT-K), form A did not offer improved chemical stability during acid hydrolysis (high-performance liquid chromatography data). Rather, impurity C exhibited higher thermal stability and aqueous stability compared to other RLT solid forms in an acidic medium. [ABSTRACT FROM AUTHOR]

Ionic liquid (IL) salt of active pharmaceutical ingredient (API) represents a promising formulation strategy to address low drug solubility and polymorphism prevalent in API solid crystals. The present work developed for the first time a buccal delivery system of API-IL via fast-dissolving API-IL-loaded gelatin films. Imidazolium-based ibuprofen salt was used as the model API-IL. The effects of API-IL loading and gelatin concentration on the film's (i) mechanical strength, (ii) inter-batch uniformity in the films' API payload, weight, and thickness, (iii) thermal stability, (iv) API dissolution and solubility enhancement were investigated. The plasticizer role of API-IL was evident, where minimum 30 wt% API-IL loading was needed to produce flexible yet mechanically-strong films. Lower API-IL loading produced brittle films due to insufficient plasticization facilitated by hydrogen bond interactions between API-IL and gelatin. Gelatin concentration influenced films' mechanical strength, weight/thickness, and API dissolution rate. Depending on the API-IL loading and gelatin concentration, films with API payload (7–30 mg/cm2), thickness (300–900 µm), and weight (20–110 mg/cm2) were produced at nearly 100% efficiency and high inter-batch uniformity. API-IL existed as amorphous liquid in the film exhibiting fast API dissolution (100% in 15 min) and high kinetic solubility (8 times thermodynamic solubility) in simulated saliva fluid. [Display omitted] • API-IL's plasticizing effect is owed to hydrogen bond interaction with gelatin. • Minimum threshold in API-IL loading exists to produce flexible yet robust films. • API-IL loading affects film's mechanical strength and thermal stability. • Gelatin concentration affects films' strength, dissolution, weight and thickness. • API-IL is amorphous in the film with fast dissolution and high kinetic solubility. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the possible pH-dependent interaction of ribociclib succinate with acid-reducing agents, which are concomitantly administered as supportive care medicines in cancer. Quality by Design-based analytical method development for a weakly basic drug ribociclib succinate supposedly having the characteristic ability of pH-dependent solubility was carried out for analyzing micro-dissolution experiment samples in biorelevant media to study pH-dependent interaction. An accurate and robust analytical method was developed using a three-level three-factorial box–behnken design for quantification of ribociclib succinate in micro-dissolution samples by the implementation of the Analytical Quality by Design approach. Here, pH of aqueous mobile phase and flow rate proved to be critical process parameters. The gastric compartment solubility was found to be 814.05 μg/mL, which dropped down to 494.71 μg/mL after a pH shift from pH 1.2–6.5. In the intestinal compartment, initial solubility was 717.58 μg/mL, which reduced to 463.20 μg/mL after a pH shift from 6.5 to 6.8. Concluded results state that pH shift does not impact the solubility or the absorption of the drug to a significant extent in the presence of acid-reducing agents. However, the study would prove to be a practical approach for examination of the behavior of the drugs at the initial stages. [ABSTRACT FROM AUTHOR]

A Biopharmaceutics Classification System (BCS)-based biowaiver monograph is presented for isavuconazonium sulfate. A BCS-based biowaiver is a regulatory option to substitute appropriate in vitro data for in vivo bioequivalence studies. Isavuconazonium sulfate is the prodrug of isavuconazole, a broad-spectrum azole antifungal indicated for invasive fungal infections. While the prodrug can be classified as a BCS Class III drug with high solubility but low permeability, the parent drug can be classified as a BCS Class II drug with low solubility but high permeability. Interestingly, the in vivo behavior of both is additive and leads isavuconazonium sulfate to act like a BCS class I drug substance after oral administration. In this work, experimental solubility and dissolution data were evaluated and compared with available literature data to investigate whether it is feasible to approve immediate release solid oral dosage forms containing isavuconazonium sulfate according to official guidance from the FDA, EMA and/or ICH. The risks associated with waiving a prodrug according to the BCS-based biowaiver guidelines are reviewed and discussed, noting that current regulations are quite restrictive on this point. Further, results show high solubility but instability of isavuconazonium sulfate in aqueous media. Although experiments on the dissolution of the capsule contents confirmed 'very rapid' dissolution of the active pharmaceutical ingredient (API) isavuconazonium sulfate, its release from the commercial marketed capsule formulation Cresemba is limited by the choice of capsule shell material, providing an additional impediment to approval of generic versions via the BCS-Biowaiver approach. [ABSTRACT FROM AUTHOR]

The short precorneal residence time of ophthalmic drops is associated with their low absorption; therefore, the development of ocular inserts capable of prolonging and controlling the ophthalmic release of drugs is an interesting option in the design and development of these drugs. A surface response design was developed, specifically the Central Composite Design (CCD), to produce ophthalmic films loaded with Dexamethasone (DEX) by the solvent evaporation method having experimental levels of different concentrations of previously selected polymers (PVP K-30 and Eudragit RS100.). Once optimization of the formulation was obtained, the in vivo test was continued. The optimal formulation obtained a thickness of 0.265 ± 0.095 mm, pH of 7.11 ± 0.04, tensile strength of 15.50 ± 3.94 gF, humidity (%) of 22.54 ± 1.7, mucoadhesion strength of 16.89 ± 3.46 gF, chemical content (%) of 98.19 ± 1.124, release of (%) 13,510.71, and swelling of 0.0403 ± 0.023 g; furthermore, in the in vivo testing the number and residence time of PMN cells were lower compared to the Ophthalmic Drops. The present study confirms the potential use of polymeric systems using PVPK30 and ERS100 as a new strategy of controlled release of ophthalmic drugs by controlling and prolonging the release of DEX at the affected site by decreasing the systemic effects of the drug. [ABSTRACT FROM AUTHOR]

Cataract surgery interventions are constantly increasing, particularly among adult and elderly patients. This type of surgery can lead to inflammatory states of the ocular anterior segment (AS), usually healed via postoperative treatment with dexamethasone (DEX)-containing eye drops. The application of eye drops is challenging due to the high number of daily administrations. In this study, mucoadhesive nanoparticles (NPs) were formulated to improve the residence time of DEX on the corneal mucosa, enhancing the drug's solubility and bioavailability. The NPs were generated using an ionotropic gelation technique, exploiting the interaction between the cationic group of chitosan (CS) and the anionic group of sulfobutylether-β-cyclodextrin (SBE-β-CD). The formation of the inclusion complex and its stoichiometry were studied through phase solubility studies, Job's plot method, and Bi-directional transport studies on MDCKII-MDR1. The obtained NPs showed good chemical and physical characteristics suitable for drug loading and subsequent testing on animal mucosa. The DEX-loaded CS/SBE-β-CD NPs exhibited a prolonged residence time on animal mucosa and demonstrated enhanced drug permeability through the corneal membrane, showing a sustained release profile. The developed NPs posed no irritation or toxicity concerns upon local administration, making them an optimal and innovative drug delivery system for inflammatory AS diseases treatment. [ABSTRACT FROM AUTHOR]

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. [ABSTRACT FROM AUTHOR]

The encapsulation of drugs within mesoporous silica (MS) has for several years been a subject of research. Previous studies proposed that drug loadings up to the monomolecular loading capacity (MLC) are the optimal choice for maintaining the drug in an amorphous form, whereas filling the pores above the monolayer and up to the pore filling capacity (PFC) may introduce some physical instabilities. The aim of this study was to assess the effect of drug loading in MS-based amorphous formulations on the stability of the amorphous form of the drug as well as the dissolution. In particular, the following drug loadings were investigated: below MLC, at MLC, between MLC and PFC and at PFC. The drug-loaded MS formulations were analyzed directly after preparation and after 18 months of storage under accelerated conditions (40 °C in both dry and humid conditions). The MLC and PFC for the drug celecoxib (CEL) on the MS ParteckSLC500 (SLC) were determined at 33.5 wt.% and 48.4 wt.%, respectively. This study found that SLC can effectively preserve the amorphous form of the drug for 18 months, provided that the loading is below the PFC (<48.4 wt.%) and no humidity is present. On the other hand, drug loading at the PFC showed recrystallization even when stored under dry conditions. Under humid conditions, however, all samples, regardless of drug loading, showed recrystallization upon storage. In terms of dissolution, all freshly prepared formulations showed supersaturation. For drug loadings below PFC, a degree of supersaturation (DS) around 15 was measured before precipitation was observed. For drug loadings at PFC, the DS was found to be lower and only 6-times compared to the crystalline solubility. Lastly, for those samples that remained amorphous during storage for 18 months, the release profiles were found to be the same as the freshly loaded samples, with similar Cmax, Tmax and dissolution rate. [ABSTRACT FROM AUTHOR]

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules. [ABSTRACT FROM AUTHOR]

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field. [ABSTRACT FROM AUTHOR]

Purpose: To revise the IVIVC considering the physiologically sound Finite Absorption Time (F.A.T.) and Finite Dissolution Time (F.D.T.) concepts. Methods: The estimates τ and τd for F.A.T. and F.D.T., respectively are constrained by the inequality τd ≤ τ; their relative magnitude is dependent on drug's BCS classification. A modified Levy plot, which includes the time estimates for τ and τd was developed. IVIVC were also considered in the light of τ and τd estimates. The modified Levy plot of theophylline, a class I drug, coupled with the rapid (30 min) and very rapid (15 min) dissolution time limits showed that drug dissolution/absorption of Class I drugs takes place in less than an hour. We reanalyzed a carbamazepine (Tegretol) bioequivalence study using PBFTPK models to reveal its complex absorption kinetics with two or three stages. Results: The modified Levy plot unveiled the short time span (~ 2 h) of the in vitro dissolution data in comparison with the duration of in vivo dissolution/absorption processes (~ 17 h). Similar results were observed with the modified IVIVC plots. Analysis of another set of carbamazepine data, using PBFTPK models, confirmed a three stages absorption process. Analysis of steady-state (Tegretol) data from a paediatric study using PBFTPK models, revealed a single input stage of duration 3.3 h. The corresponding modified Levy and IVIVC plots were found to be nonlinear. Conclusions: The consideration of Levy plots and IVIVC in the light of the F.A.T. and F.D.T. concepts allows a better physiological insight of the in vitro and in vivo drug dissolution/absorption processes. [ABSTRACT FROM AUTHOR]

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray–antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer–Peppas kinetic model. In summary, the co-spray–antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials. [ABSTRACT FROM AUTHOR]

Objectives: Liquisolid tablets are an innovative approach to enhance the dissolution rate and, thereby, the bioavailability of therapeutic agents with poor aqueous solubility. Materials and Methods: The objective of the current research was to compare the bioavailability of the optimized formulation of the olanzapine (OLZ) liquisolid tablet with that of the marketed tablet (MT) by conducting pharmacokinetic and behavioral assessment studies. Ten formulations were designed using Kolliphor EL as a non-volatile solvent, and the respective tablets were prepared by the direct compression method. Results: Pre-compression studies of powders of all the formulations showed good/excellent flow properties and compressibility. The drug release profiles of liquisolid tablets were determined and compared with those of MT. Based on the in vitro results, K250 was considered as an optimized formulation and selected for further in vivo studies. AUC0-∞ value of K250 formulation was found to be 357.2 ± 35.5 ng.h.mL-1, which was higher than that of the MT (258.4 ± 29.9 ng.h.mL-1). The reduction in locomotor activity was enhanced remarkably in K250 compared with MTs at p < 0.05. The time periods taken to fall in the rotarod test were approximately equal in the experimental groups, which indicated the absence of extrapyramidal side effects. There was a remarkable decrease in the number of boxes covered in the open field test. Conclusion: Kolliphor EL was found to be a potential non-volatile solvent that can be used to produce liquisolid tablets of OLZ with improved flow, compressibility, dissolution, and bioavailability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Astaxanthin (AST) is approved by the US Food and Drug Administration (FDA) as a safe dietary supplement for humans. As a potent lipid‐soluble keto‐carotenoid, it is widely used in food, cosmetics, and the pharmaceutical industry. However, its low solubility limits its powerful biological activity and its application in these fields. This study aims to develop a delivery system to address the low solubility and bioavailability of AST and to enhance its antioxidant capacity. RESULTS: Astaxanthin‐loaded composite micelles were successfully prepared via coaxial electrospray technology. Astaxanthin existed in the amorphous state in the electro‐sprayed formulation with an approximate particle size of 186.28 nm and with a polydispersity index of 0.243. In this delivery system, Soluplus and copovidone (PVPVA 64) were the main polymeric matrix for AST, which then released the drug upon contact with aqueous media, resulting in an overall increase in drug solubility and a release rate of 94.08%. Meanwhile, lecithin, and Polyethylene glycol‐grafted Chitosan (PEG‐g‐CS) could support the absorption of AST in the gastrointestinal tract, assisting transmembrane transport. The relative bioavailability reached about 308.33% and the reactive oxygen species (ROS) scavenging efficiency of the formulation was 44.10%, which was 1.57 times higher than that of free astaxanthin (28.10%) when both were at the same concentration level based on astaxanthin. CONCLUSION: Coaxial electrospray could be applied to prepare a composite micelles system for the delivery of poorly water‐soluble active ingredients in functional food, cosmetics, and medicine. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms in vivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug–drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended‐release formulations, where systemic exposure of nifedipine was increased in subjects after multiple‐dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well‐understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically‐based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in in vitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two‐stage in vitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple‐dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4‐mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH‐dependent formulation. The reported model‐based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations. [ABSTRACT FROM AUTHOR]

Sparsentan is a dual endothelin/angiotensin II receptor antagonist indicated to reduce proteinuria in patients with primary IgA nephropathy at high risk of disease progression. In vitro data indicate that sparsentan is likely to inhibit or induce various CYP enzymes at therapeutic concentrations. Sparsentan as a victim and perpetrator of CYP3A4 mediated drug–drug interactions (DDIs) has been assessed clinically. A mechanistic, bottom‐up, physiologically‐based pharmacokinetic (PK) model for sparsentan was developed based on in vitro data of drug solubility, formulation dissolution and particle size, drug permeability, inhibition and induction of metabolic enzymes, and P‐glycoprotein (P‐gp) driven efflux. The model was verified using clinical PK data from healthy adult volunteers administered single and multiple doses in the fasted and fed states for a wide range of sparsentan doses. The model was also verified by simulation of clinically observed DDIs. The verified model was then used to test various DDI simulations of sparsentan as a perpetrator and victim of CYP3A4 using an expanded set of inducers and inhibitors with varying potency. Additional perpetrator and victim DDI simulations were performed using probes for CYP2C9 and CYP2C19. Simulations were conducted to predict the effect of complete inhibition of P‐gp inhibition on sparsentan absorption and clearance. The predictive simulations indicated that exposure of sparsentan could increase greater than two‐fold if co‐administered with a strong CYP3A4 inhibitor, such as itraconazole. Other potential DDI interactions as victim or perpetrator were all within two‐fold of control. The effect of complete P‐gp inhibition on sparsentan PK was negligible. [ABSTRACT FROM AUTHOR]

This work presents the application of L-tartaric acid (L-TA), ascorbic acid (AA), and L-carnitine (L-CAR) as a safe and non-toxic alternative agent to enhance the aqueous solubility of baclofen (BAC). The solvent evaporation method was employed for co-crystallization in three stoichiometric ratios of the drug, coformer (1:1, 1:3, 1:5) and formulations were confirmed by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR). DSC study revealed the presence of both endothermic and exothermic peaks in compounds containing AA and L-TA. With respect to the BAC, L-TA and BAC, AA, the appearance of new diffraction peaks that do not overlap with un-processed BAC may be the implication of a new structure. The intensity of some diffraction peaks disappeared or reduced significantly which may also imply the formation of a new crystal phase. The solubility of the multicomponents increased and surpassed the solubility of BAC. Overall, the new compounds show significantly higher drug solubility whereas their physical mixtures only demonstrate a marginal increase in BAC solubility. The high solubility records of BAC, AA and BAC, L-TA evidence the marked difference in solubility of the new compounds with respect to their physical mixtures. The saturation solubility of BAC, L-CAR compound did not show any improvement relative to the un-processed BAC. These findings confirm that a new crystal phase may not have been obtained during the co-crystallization of BAC and L-CAR. [ABSTRACT FROM AUTHOR]

The aim of this study is to demonstrate the effect of stoichiometry upon characteristics of quercetin-arginine (QCT-Arg) cocrystals. Quercetin (QCT) is a most abundant flavonoid in vegetables and fruits and has been widely used as an antioxidant. However, its oral bioavailability remains low due to poor aqueous solubility. We illustrate that QCT-Arg cocrystals formulated through an optimized stoichiometry can be a useful approach for its solubilization. Cocrystals were prepared using solvent evaporation method. Characterizations were performed through microscopic, spectroscopic, and thermal techniques. The stoichiometry was confirmed from the binary phase diagram which was prepared using thermograms derived from differential scanning calorimetric experiments. Cocrystal formation was accompanied by the conversion of isotropic phase into anisotropic one. Thread-like cocrystals were formed, regardless of QCT-Arg stoichiometry and solvent's polarity. Spectral analyses suggested that cocrystal structure was held together by hydrogen bonding between QCT and Arg. We ruled out the existence of eutectic mixture based on the observation of two eutectic points in the binary phase diagram. Morphology of cocrystals remained unaffected by the solvent type, stoichiometry and the presence of surfactant. We noticed that the cocrystals could improve the aqueous solubility of QCT. [ABSTRACT FROM AUTHOR]

The best solubility enhancement approach is phospholipids complexation. It has been effectively employed by a number of writers to enhance the permeability, oral bioavailability, and solubility of several medicinal substances. The meloxicam is a member of BCS Class II, and because of its poor solubility and high permeability, its clinical application may have been constrained. Therefore, it is necessary to use a method that modifies the biopharmaceutical features. In this work, meloxicam, an NSAID with demonstrated anticancer action, was combined with phospholipid to increase its solubility. Utilizing solvent evaporation, the meloxicam phospholipid complex was produced. Particle size, zeta potential, SEM analysis, in vitro drug release, and solubility were assessed for the produced complex. The results obtained in this study showed the smaller particle size in nanometer range and physical stability with desired zeta potential. Meloxicam's prolonged release from the phospholipid complex is demonstrated by the in vitro drug release investigation. The apparent solubility analysis of meloxicam phospholipid complex. Pure meloxicam showed that the drug's solubility was several times higher than that of the pure form. Hence in conclusion we can say that the phospholipid complexation could be the ideal method for solubility enhancement of drug like meloxicam. [ABSTRACT FROM AUTHOR]

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases like HIV/AIDS. Etravirine is one of the key components of highly active antiretroviral therapy used for the treatment of HIV-1 infections. The aim of the present study was to formulate and evaluate nanostructured lipid carriers of etravirine, intended for targeted delivery to macrophages, using solvent emulsification - evaporation technique. Estimates of drug solubility were employed for selection of solid lipids, liquid lipids and stabilizers for the preparation of NLCs. Design of experiments was used to optimize the formulation with respect to drug-lipid ratio and concentration of stabilizer in the external phase using 32 full factorial design. Particle size of the carriers and drug release characteristics were the responses which were set to suitable levels for optimization. The optimized formulation was prepared and characterized for size, poly dispersity index, zeta potential, entrapment efficiency and appearance. The nanostructured lipid carriers of etravirine were prepared using stearylamine and glyceryl monostearate as solid lipids, Capryol 90 as liquid lipid and polyvinyl pyrrolidone as stabilizer. All experimental batches showed high drug loading efficiencies nearing 99%, indicating that etravirine remained closely associated with the lipids. The nanostructured lipid carriers displayed a zeta potential of -10.1 mv and a particle size of 261.6 nm with a polydispersity index of 0.374. In vitro release of etravirine from the optimized formulation at 2 h was 9% indicative of a low burst; and 56% of the entrapped drug was released after 24 h, suggesting prolonged release characteristics. Thus, etravirine loaded lipidic nanoparticles with potential for targeting cellular reservoirs of the AIDS virus such as macrophages were successfully developed. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding. [ABSTRACT FROM AUTHOR]

Background: Globally, millions of people have been affected by fraudulent pharmaceutical products, particularly those in developing countries. Although the problem of falsified and substandard drugs is acknowledged, the extent of the issue is ever-changing, has a dynamic nature, and should be quantified and captured in a recent snapshot. Objective: This systematic review seeks to examine the data that can quantify and provide a current snapshot of the prevalence of SF antimicrobials in selected east Africa countries. Methods: Scientific studies on antimicrobial quality were searched in PubMed, Embase, Scopus, and Google Scholar from 2017 to February 2023. The search strategy focused on scientific articles published in peer-reviewed scientific journals written in English and the studies exclusively done in any of the selected countries of east Africa. The articles were carefully reviewed by two individuals for inclusion independently, first by title followed by abstract and the full-text retrieval. To minimize bias associated with the methodology used for data collection, the quality of the studies was assessed for quality according to the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). The reporting of this systematic review was done following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: Fifteen studies that estimated the prevalence of poor-quality antimicrobial medicines in selected four east African countries were included. The overall percentage of samples of antimicrobials that failed at least one quality test was 22.6% (151/669) with each class's prevalence of 17% in antibiotics (73/432), 24% in antimalarial (41/171), and 56% in anthelmintics (37/66). Quality control parameters of API content were the most commonly examined in the included studies, accounting for 14/15 (93%) studies. Fifty (33.1%) of the failing samples failed assay API- content determination, while 26.5% (n = 40) failed the visual inspection and packaging analysis; 19.2% (29) failed dissolution; 14% (n = 21) flawed hardness or friability; 4%(n = 6) failed uniformity, as well as 3.2% (n = 5) failed disintegration test of the quality control parameter. Conclusion: It was found that this review was general in these selected east African countries and was a catalyst for combating the menace of poor-quality medications that affect millions of lives. [ABSTRACT FROM AUTHOR]

The solubility, permeability, and dissolution rate of an active pharmaceutical ingredient (API) are critical factors in determining its pharmacokinetic performance in oral dosage forms. Modifying these properties can potentially enhance the drug's pharmacokinetics. Vandetanib (VDTB), classified as a class II anti-cancer drug in the biopharmaceutical classification system (BCS), suffers from low solubility (0.008 mg mL−1) and an extended pharmacokinetic half-life (19 days), necessitating the administration of high doses, which leads to undesirable side effects. To address this issue, we have employed a crystal engineering approach to enhance the solubility of VDTB. We employed the liquid-assisted grinding (LAG) method followed by the slow evaporation technique to prepare novel solid forms of VDTB by incorporating various aliphatic dicarboxylic acids, including succinic acid (SUA), adipic acid (ADA), pimelic acid (PIA), azelaic acid (AZA), and sebacic acid (SBA). These newly obtained solid forms were characterized by SC-XRD, PXRD, TGA, and DSC experiments. The crystal structure analyses revealed a proton transfer between the carboxylic acid group of aliphatic acids and the N-methyl piperidine moiety of VDTB, confirming salt/adduct formation. Additionally, all of the molecular salts were stabilized by charge-assisted N+–H⋯O− hydrogen bonds, while the parent VDTB crystal structure is stabilised by N–H⋯N interactions. Moreover, the solubility and dissolution rate of these new solid forms were assessed in a pH 7.4 phosphate buffer medium, with the results indicating that all of the solid forms, except for VDTB:SBA, exhibited higher solubility compared to pure VDTB. These findings offer promising prospects for the development of an improved VDTB formulation with enhanced pharmacokinetic properties. [ABSTRACT FROM AUTHOR]

Recently, the co-crystallization of pharmaceutical drugs is gaining consideration because it is an environmentally friendly and potentially effective technique to improve the solubility and bioavailability of poorly soluble drugs without altering the chemical identity or reducing the biological activity or therapeutic effect of the active pharmaceutical ingredient (API). The co-crystallization process in the pharmaceutical industry is still not fully utilized owing to the limited methods for large-scale production. However, it is a very convenient, appropriate, and green technique in the field of drug development research as only a few synthetic steps are involved with the minimal or no use of solvents. Herein, the selection criteria or the factors that affect the selection of coformers in this process are discussed. In addition, the different stages of co-crystal manufacturing, from the screening phase to industrial production, are identified and the use of continuous and scalable methods in co-crystal production as well as the implementation of quality-by-design and process analytical technology concepts are addressed. The potential pharmaceutical applications, like the enhancement in drug solubility, and the drug dissolution rate, which consequently leads to improved bioavailability and therapeutic efficacy, are also highlighted. This study briefly reviews different strategies for enhancing the solubility of poorly soluble drugs with a special emphasis on co-crystal formation, including solvent-based and solvent-free methods of production. [ABSTRACT FROM AUTHOR]

Background: The current challenge in drug development lies in addressing the physicochemical issues that lead to low drug effectiveness. Solubility, a crucial physicochemical parameter, greatly influences various biopharmaceutical aspects of a drug, including dissolution rate, absorption, and bioavailability. Amorphous solid dispersion (ASD) has emerged as a widely explored approach to enhance drug solubility. Objective: The objective of this review is to discuss and summarize the development of polyvinylpyrrolidone (PVP)-based amorphous solid dispersion in improving the physicochemical properties of drugs, with a focus on the use of PVP as a novel approach. Methodology: This review was conducted by examining relevant journals obtained from databases such as Scopus, PubMed, and Google Scholar, since 2018. The inclusion and exclusion criteria were applied to select suitable articles. Results: This study demonstrated the versatility and efficacy of PVP in enhancing the solubility and bioavailability of poorly soluble drugs. Diverse preparation methods, including solvent evaporation, melt quenching, electrospinning, coprecipitation, and ball milling are discussed for the production of ASDs with tailored characteristics. Conclusion: PVP-based ASDs could offer significant advantages in the formulation strategies, stability, and performance of poorly soluble drugs to enhance their overall bioavailability. The diverse methodologies and findings presented in this review will pave the way for further advancements in the development of effective and tailored amorphous solid dispersions. [ABSTRACT FROM AUTHOR]

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs. [ABSTRACT FROM AUTHOR]

Computational methods play a pivotal role in the pursuit of efficient drug discovery, enabling the rapid assessment of compound properties before costly and time-consuming laboratory experiments. With the advent of technology and large data availability, machine and deep learning methods have proven efficient in predicting molecular solubility. High-precision in silico solubility prediction has revolutionized drug development by enhancing formulation design, guiding lead optimization, and predicting pharmacokinetic parameters. These benefits result in considerable cost and time savings, resulting in a more efficient and shortened drug development process. The proposed SolPredictor is designed with the aim of developing a computational model for solubility prediction. The model is based on residual graph neural network convolution (RGNN). The RGNNs were designed to capture long-range dependencies in graph-structured data. Residual connections enable information to be utilized over various layers, allowing the model to capture and preserve essential features and patterns scattered throughout the network. The two largest datasets available to date are compiled, and the model uses a simplified molecular-input line-entry system (SMILES) representation. SolPredictor uses the ten-fold split cross-validation Pearson correlation coefficient R 2   0.79 ± 0.02 and root mean square error (RMSE) 1.03 ± 0.04 . The proposed model was evaluated using five independent datasets. Error analysis, hyperparameter optimization analysis, and model explainability were used to determine the molecular features that were most valuable for prediction. [ABSTRACT FROM AUTHOR]

Phytochemicals have shown potentials in preventing and treating various lung diseases, including asthma and lung cancer. However, their use has been hampered by limitations such as poor water solubility and instability. Nanoformulations, which include organic nanoparticles (e.g. liposomes) and inorganic nanoparticles (e.g. gold/silver nanoparticles) have potential to enhance drug solubility and subsequently increase their absorption and bioavailability. These drug formulations can be administered via various routes such as oral, intravenous, and pulmonary. This review highlights the potential of some phytochemicals in managing lung diseases and discusses the mechanism of actions of these phytochemicals and the impact of using the nanoformulations to deliver phytochemicals, particularly through pulmonary route. While pre-clinical studies have shown promising therapeutic activities of phytochemicals-loaded nanoformulations, further research is required. In conclusion, the application of phytochemicals and nanoformulations as drug delivery systems could be a promising approach to facilitate optimal therapy for lung diseases. [ABSTRACT FROM AUTHOR]

Aim: Objective of work was to compare role of β-Cyclodextrin (β-CD) and Nanosponges (NS) prepared with different cross-linking ratios and different drug loading ratios to enhance solubility and dissolution rate of Albendazole (ALB). Materials and Methods: Diphenyl Carbonate (DPC) was used as cross-linker for preparing NS with various β-CD and DPC ratios (1:2 and 1:4). Solvent evaporation was used to make binary complex. ALB and NS were dissolved in Dichloromethane (DCM) in 1:1 and 1:2 ratios and triturated until solvent evaporated. Phase solubility, saturation solubility and in vitro dissolution studies were performed. Solid state characterization as well as spectral and thermal analyses was done. Results: Stability constant for complexes ALB-β-CD, ALB-NS (1:2 ratios) and ALB-NS (1:4 ratios) were found to be 1715M-1±18.3, 1902M-1±29.5 and 1945M-1±30.1 respectively. Maximum solubility of all complexes was observed in fed state simulated intestinal fluid (FeSSIF). The increase was to the tune of 3-8 folds for all binary complexes at 1:1 and 1: 2 drug loading ratios. Dissolution rate increased by 47%-67% for drug loading ratio 1:1 and 55-71% for drug loading ratio 1:2 in FeSSIF in 150 min. Conclusion: β-CD based NS improved solubility of ALB. Presence of drug in molecular form in nanochannels and amorphization were responsible for increase in solubility. Nanosponges prepared in ratio 1:4 and drug loading in ratio 1:2 showed highest increase in solubility and dissolution rate. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to develop a stable and effective form of an Orodispersible tablet containing Nicardipine Hydrochloride for the immediate treatment of high blood pressure and angina. The aim was to achieve this by using the natural sweetener stevia to improve taste. Background: Nicardipine Hydrochloride is used to treat high blood pressure and angina. However, currently available immediate release forms have limitations in terms of drug release and taste. Therefore, the goal was to develop an Orodispersible form of the drug that would enhance drug release and improve taste masking capabilities. Materials and Methods: We developed formulations of Nicardipine Hydrochloride Orodispersible tablets using the natural sweetener Stevia rebaudiana to enhance taste and reduce the caustic sensation. We confirmed the compatibility of the drug-excipient mixture using FTIR. Drug content and dissolution were determined through UV spectrophotometry. We also conducted organoleptic tests and other compendial specification tests. Precompression parameters were evaluated, and measures were taken to improve the flow behavior of the formulation blend by using excipients with excellent flow properties. Based on disintegration and dissolution time, we selected the F6 formulation as the optimized formula. We then subjected the developed trial to stability studies for three months, evaluating disintegration time, drug content, and dissolution. Results: The optimized formulation demonstrated a disintegration time of 46.25±0.85 sec and a dissolution rate of 100.50±2.50. Compendial tests remained stable without any significant fluctuations after the stability study. Also, the taste of the drug was pleasant after taste. Conclusion: Through the appropriate selection of excipients, we successfully developed a stable and effective form of Nicardipine Hydrochloride Orodispersible tablet with enhanced drug release (using the solid dispersion technique) and improved taste masking capabilities. The optimized formulation yielded favorable results in terms of disintegration and dissolution time, drug content, and stability. [ABSTRACT FROM AUTHOR]