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Purpose: The objective of the present study was to prepare a solid self-nano emulsifying drug delivery system (S-SNEDDS) of Fimasartan Potassium Trihydrate (FPT), a poorly water-soluble antihypertensive agent. Methods: Equilibrium Solubility study and ternary phase diagram study were conducted for screening of excipients. D-optimal Mixture design was employed to optimise the formulation variables, X1 (amount of oil; Capmul MCM C8), X2 (amount of surfactant; Labrasol) and X3 (amount of co-solvent; Transcutol HP). Self-emulsification time (Y1), percentage transmittance (Y2) and mean globule size (Y3) were set as response variables. Optimised liquid SNEDSS (L-SNEDDS) formulation was further assessed for robustness to dilution, thermodynamic stability study, cell viability and TEM analysis. L-SNEDDS was converted into free flowing powder (S-SNEDDS) by adsorption on the porous carrier like Neusilin US2 and thereafter filled in hard gelatin capsules (HGC). Prepared HGC was further evaluated for in-vitro dissolution, stability and bioavailability study. Results: The optimized L-SNEDDS formulation consists of 20% oil, 40% surfactant, and 40% co-solvent, demonstrating strong thermodynamic stability and safety for cellular use.TEM analysis demonstrated that the nanoemulsion comprised spherical, uniformly sized globules. When testing the in vitro dissolution of HGC derived from FPT-loaded S-SNEDDS, there was a noticeable increase in the drug's dissolution rate, achieving 98% drug release within 30 min. Additionally, subsequent stability testing in accordance with ICH guidelines over a six-month period indicated that the HGC remained stable, with no significant alterations in its physicochemical characteristics. The bioavailability study indicated a significant enhancement, with a 1.5-fold increase in the relative bioavailability of S-SNEDDS in comparison to the pure drug. Conclusion: Based on the results obtained, it has been concluded that S-SNEDDS, with its ability to create a nanometric dispersion of controllable size, enhances the solubility, dissolution, bioavailability and stability of the encapsulated FPT drug more effectively than conventional dosage forms. Present study demonstrated an increase in dissolution and improved bioavailability for FPT. In conclusion, the results of this study indicate the potential use of the developed S-SNEDDS formulation for delivering the active ingredient. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to broaden the knowledge on co-amorphous phospholipid systems (CAPSs) by exploring the formation of CAPSs with a broader range of poorly water-soluble drugs, celecoxib (CCX), furosemide (FUR), nilotinib (NIL), and ritonavir (RIT), combined with amphiphilic phospholipids (PLs), including soybean phosphatidylcholine (SPC), hydrogenated phosphatidylcholine (HPC), and mono-acyl phosphatidylcholine (MAPC). Methods: The CAPSs were initially prepared at equimolar drug-to-phospholipid (PL) ratios by mechano-chemical activation-based, melt-based, and solvent-based preparation methods, i.e., ball milling (BM), quench cooling (QC), and solvent evaporation (SE), respectively. The solid state of the product was characterized by X-ray powder diffraction (XRPD), polarized light microscopy (PLM), and differential scanning calorimetry (DSC). The long-term physical stability of the CAPSs was investigated at room temperature under dry conditions (0% RH) and at 75% RH. The dissolution behavior of the CCX CAPS and RIT CAPS was studied. Results: Our findings indicate that SE consistently prepared CAPSs for CCX-PLs, FUR-PLs, and RIT-PLs, whereas the QC method could only form CAPSs for RIT-PLs, CCX-SPC, and CCX-MAPC. In contrast, the BM method failed to produce CAPSs, but all drugs alone could be fully amorphized. While the stability of each drug varied depending on the PLs used, the SE CAPS consistently demonstrated the highest stability by a significant margin. Initially, a 1:1 molar ratio was used for screening all systems, though the optimal molar ratio for drug stability remained uncertain. To address this, various molar ratios were investigated to determine the ratio yielding the highest amorphous drug stability. Our results indicate that all systems remained physically stable at a 1.5:1 ratio and with excess of PL. Furthermore, the CAPS formed by the SE significantly improves the dissolution behavior of CCX and RIT, whereas the PLs provide a slight precipitation inhibition for supersaturated CCX and RIT. Conclusions: These findings support the use of a 1:1 molar ratio in screening processes and suggest that CAPSs can be effectively prepared with relatively high drug loads compared to traditional drug–polymer systems. Furthermore, the study highlights the critical role of drug selection, the preparation method, and the PL type in developing stable and effective CAPSs. [ABSTRACT FROM AUTHOR]

Lopinavir (LPV) and ritonavir (RTV) are two of the essential antiretroviral active pharmaceutical ingredients (APIs) characterized by poor solubility. Hence, attempts have been made to improve both their solubility and dissolution rate. One of the most effective approaches used for this purpose is to prepare amorphous solid dispersions (ASDs). To our best knowledge, this is the first attempt aimed at developing ASDs via the electrospinning technique in the form of fibers containing LPV and RTV. In particular, the impact of the various polymeric carriers, i.e., Kollidon K30 (PVP), Kollidon VA64 (KVA), and Eudragit® E100 (E100), as well as the drug content as a result of the LPV and RTV amorphization were investigated. The characterization of the electrospun fibers included microscopic, DSC, and XRD analyses, the assessment of their wettability, and equilibrium solubility and dissolution studies. The application of the electrospinning process led to the full amorphization of both the APIs, regardless of the drug content and the type of polymer matrix used. The utilization of E100 as a polymeric carrier for LPV and KVA for RTV, despite the beads-on-string morphology, had a favorable impact on the equilibrium solubility and dissolution rate. The results showed that the electrospinning method can be successfully used to manufacture ASDs with poorly soluble APIs. [ABSTRACT FROM AUTHOR]

Background: The goal of the current research was to use the straight forward, scalable, and economical Liquisolid compact to improve the dissolution profile of the poorly soluble medication Ramipril. Objectives: Utilising various polymers and liquid vehicles, the study's objective was to develop and characterise Liquisolid compact. Materials and Methods: Ramipril liquisolid were formulated using Propylene glycol and PEG 400 as liquid vehicle, MCC as a carrier, Aerosil 200 as a coating material. By using differential scanning calorimetry, the crystallinity of the newly developed drug formulation and the interactions between excipients were investigated. No interaction between the medication and excipients was established by FTIR tests. Results: The friability, hardness, weight variation, disintegration test, and in vitro dissolution investigations of all formed systems were evaluated for post-compression parameters. The optimized F9 formulation showed better results in vitro dissolution of 97.91% at 60 min, when compared with the marketed which showed 77.28% at 60 min. Conclusion: The drug release rates from liquisolid compacts were substantially higher than those from commercial formulations, which points to a potential strategy for speeding up the breakdown of medications that aren't very water-soluble. [ABSTRACT FROM AUTHOR]

Objectives: Nanosuspensions are increasingly recognized as a valuable technology for enhancing poorly water-soluble drugs' solubility and dissolution rate, thereby improving their bioavailability. In this study, we employed ultrasonic-assisted precipitation to fabricate nanosuspensions of indomethacin (IND), utilizing Soluplus® (Sol) as a stabilizing agent. Our objectives were driven by hypotheses centered on optimizing formulation variables and developing predictive models for optimal IND formulations. Significance: This research highlights the Box-Behnken design (BBD) as a powerful tool that optimizes the properties of IND nanosuspensions, thus significantly enhancing their dissolution rate. Methods: The impacts of the independent variables on the mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were investigated using BBD. The optimized nanosuspension was freeze-dried with 3% trehalose to produce a dry nanosuspension (DNS). The DNS was characterized by SEM, DSC, XRPD, solubility, and dissolution. Results: The IND: Sol ratio and sonication power significantly affected the MPS and ZP of the nanosuspensions. The optimized formulation showed MPS, PDI, and ZP of 144.77 ± 6.68 nm, 0.26 ± 0.08, and −24.6 ± 1.90 mV, respectively. The DNS exhibited spherical particle morphology. The DSC and XRPD confirmed the amorphous state of IND with enhanced solubility and dissolution of IND. DNS showed a 3.7-fold increase in drug release in the first 15 min compared with raw IND. Conclusions: This study demonstrated the critical role of BBD in accurately predicting the values of independent variables essential for formulating optimal nanosuspensions. These formulations possess specific properties that can be effectively integrated into various dosage forms tailored for different routes of administration. [ABSTRACT FROM AUTHOR]

Background and objective: Poorly water-soluble dugs provide less dissolution rate and bioavailability; hence, it minimizes the pharmacological effect of orally administered medications. Gliclazide is a sulfonylurea antidiabetic medication of the second generation, used to treat type II diabetes mellitus. It belongs to the class II drugs of biopharmaceutic classification system, indicating that it has high permeability and poor aqueous solubility. The aim of this study is to determine an optimum solid dispersion method and drug to carrier ratio to improve the solubility of gliclazide. Methods: Solid dispersions of gliclazide were formulated with polyvinyl pyrrolidone K30 using various drug to carrier ratios (1:1, 1:3, and 1:5) by utilizing kneading and solvent evaporation methods. Solubility and dissolution rate of solid dispersion formulas were compared with pure drug and co-ground mixtures. The formulations were further evaluated in terms of percentage of yield, drug content, FTIR, SEM, DSC, and XRD studies. Results: The highest solubility improvement of gliclazide was obtained at the ratio 1:5 of gliclazide and PVP K30 utilizing solvent evaporation method, solubility increased about 2.54 folds (98.299 ± 5.77 µg/ml) as compared to pure gliclazide (38.739 µg/ml). Meanwhile, the greatest improvement in gliclazide dissolution rate was observed in the same solid dispersion formula that was about 105.76 % after 30 minutes. FTIR demonstrated no unwanted interaction between the drug and carrier. While, SEM, DSC, and XRD showed crystallinity of the drug was minimized and converted to amorphous form in solid dispersion formula. Conclusion: Based on the investigations of this study, it can be concluded that the drug to carrier weight ratios and preparation methods had the influence on the drug solubility and the release rate. The obtained data revealed that the solvent evaporation is the best method of solid dispersion for enhancing gliclazide solubility using PVP K30 with the ratio 1:5 of the drug and carrier.

Abstract To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion’s diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended. Graphical Abstract

This study endeavors to augment the aqueous solubility and dissolution profile of abiraterone acetate (ABT) through the strategic establishment of inclusion complexes with 2,6 Di-O-methyl β-cyclodextrin (DM-β-CD). Phase solubility assessments of ABT, conducted in an aqueous phase at room temperature, illuminated the impact of DM-β-CD on its solubility. Subsequently, an inclusion complex was meticulously fabricated via the solvent evaporation method. The resultant ABT-DM-β-CD inclusion complex (IC) underwent rigorous evaluation encompassing aqueous saturation solubility studies, determination of drug loading, and estimation of entrapment efficiency. The establishment of the IC was further substantiated through an array of analytical techniques, including molecular docking, Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), contact angle and in vitro dissolution studies. ABT-DM-β-CD IC was formed in a 1:1 stoichiometric ratio, resulting in substantial increase in aqueous solubility by ~ 137.51-fold. Results unveiled encapsulation efficiency and drug loading of ABT-DM-β-CD IC 90.40 ± 0.60% and 20.55 ± 0.14%, respectively. Chemical interaction through FTIR and 1H-NMR revealed the complexation occurred between ABT and DM-β-CD. Solid-state analyses indicated drug amorphization within the IC, consequentially amplifies drug solubility. The solubility profile of ABT and its IC demonstrated a remarkable enhancement in aqueous solubility, attributed to the inherent hydrophilicity of DM-β-CD. These findings underscore the potential for further investigation in the formulation and development of drug carriers tailored for the delivery of hydrophobic drugs. [ABSTRACT FROM AUTHOR]

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further. [ABSTRACT FROM AUTHOR]

Co-processed superdisintegrants have emerged as key excipients in pharmaceutical formulation development, offering solutions to challenges related to poor solubility, bioavailability, and patient compliance. This comprehensive review article provides an in-depth analysis of the principles, mechanisms, manufacturing techniques, and applications of co-processed superdisintegrants in drug delivery systems. The review highlights the role of co-processed excipients in enhancing dissolution kinetics, improving formulation efficiency, and enabling innovative drug delivery platforms such as personalized medicine and combination therapies. Regulatory considerations, quality standards, and future directions for research and innovation in this field are also discussed. Through a synthesis of current literature and insights into emerging trends, this review aims to provide researchers, formulation scientists, and pharmaceutical professionals with a comprehensive understanding of the potential and challenges associated with co-processed superdisintegrants in pharmaceutical formulations. Ultimately, the integration of co-processed excipients into formulation development holds promise for advancing drug delivery technology, improving therapeutic outcomes, and addressing unmet medical needs in patient care. [ABSTRACT FROM AUTHOR]

Developing efficient methods for cocrystal production is crucial to improving drug solubility and bioavailability. This study utilized the spherical agglomeration-co-crystallization (SA-CC) method to produce spherical ibuprofen-nicotinamide (IBU-NICO) cocrystals. This method used ethanol (ETA) as a solvent and a mixture of deionized water and PEG-4000 as an anti-solvent, enhancing the micromeritic properties of the cocrystal. The addition of dichloromethane (DCM) facilitated the formation of spherical particles via rapid viscous phase transition. Fourier-transform infrared (FTIR) spectroscopy identified significant molecular interactions, such as hydrogen bonding between the ibuprofen carboxyl and nicotinamide acylamino groups, ensuring cocrystal stability. Hot-stage microscopy (HSM) and scanning electron microscopy (SEM) analyses demonstrated that cocrystals exhibited lower thermal stability but improved dissolution rates due to their amorphous-crystalline structures and rough, porous surfaces. Differential scanning calorimetry (DSC) showed altered thermal profiles with a reduction of 7.21°C, indicating modified crystal lattice structures. Powder X-ray diffraction (PXRD) confirmed the formation of new crystalline phases. Micromeritic evaluations revealed favorable particle size distribution (PSD) with an average size of 5 mm, enhanced flowability, and compressibility, with cocrystals showing superior tensile strength (2.36 MPa at 207.97 MPa) and dissolution rates 2.82 times higher than pure IBU at pH 6.8. These findings highlight the potential of the SA-CC method to produce cocrystals with enhanced drug properties, paving the way for improved pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended. [ABSTRACT FROM AUTHOR]

Despite the antioxidant properties of lycopene, its poor water solubility reduces its efficiency and bioavailability. The study aimed to enhance the solubility of lycopene to improve its efficiency. To make lycopene more soluble, different carriers were added using physical mixing and solid-dispersion techniques. Then, the mechanisms of this solubility improvement were studied using solid-state characterization and docking studies. Out of 56 polymers and their combinations, isolated protein-whey (IWP) and polyvinylpyrrolidone-K30 (PVP-K30) showed the highest solubility for lycopene. These particles exhibited a more negative surface charge and a lower polydispersity index. Dissolution kinetics revealed that using IPW resulted in the highest release rate of lycopene. It was found that lycopene and β-lactoglobulin, an IPW component, have a hydrophobic bond. This makes a hydrophilic coating around the lycopene molecule. DSC results showed that lycopene could be in an amorphous state in IPW-lycopene formulations. The results of this study show how some food ingredients can improve the bioavailability of drugs that don't dissolve well in water. This will help with future efforts to deliver drugs. [ABSTRACT FROM AUTHOR]

Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 μm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 μm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9–10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare. [Display omitted] • dry powder inhalation of clofazimine using porous microparticle as sole excipient. • a stable formulation with high FPF indicating high drug deposition in the lungs. • micron-sized carrier dissolves in the lung fluid generating nano-sized carrier. • enhanced efficacy (MIC99) against extra- and intra-cellular mycobacteria. • in vitro safety using respiratory epithelium model, macrophages and erythrocytes. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the usage of solid dispersion (SD) to enhance the dissolution rate of the poorly soluble drug piroxicam for sublingual formulation. Poloxamer grade 407 (Kolliphor® P-407), a commercially available polymer, was chosen, and various solid dispersions with different weight ratios of piroxicam and Poloxamer were prepared using the hot melt method. Compatibility tests using FTIR spectroscopy, DSC, and XRD were conducted to assess any chemical or physical interactions between the drug and polymer. In vitro dissolution tests were performed on the solid dispersions. The results of the FTIR spectroscopy study indicated no chemical interaction between the drug and the polymer. Similarly, the DSC and XRD analyses showed no physical interaction between the drug and the polymer. The maximum cumulative percentage release of the pure drug and the solid dispersion at 15 minutes were 40.90±1.83% and 99.56±3.25%, respectively. Based on these findings, it was concluded that the solid dispersion with a ratio of 2:1 (Drug: Poloxamer-407) showed a noteworthy upsurge in the dissolution rate in comparison to the pure drug. [ABSTRACT FROM AUTHOR]

Solid dispersions are a promising approach to enhance the dissolution of poorly water-soluble drugs. Solid crystalline formulations show a fast drug dissolution and a high thermodynamic stability. To understand the mechanisms leading to the faster dissolution of solid crystalline formulations, physical mixtures of the poorly soluble drugs celecoxib, naproxen and phenytoin were investigated in the flow through cell (apparatus 4). The effect of drug load, hydrodynamics in the flow through cell and particle size reduction in co-milled physical mixtures were studied. A carrier- and drug-enabled dissolution could be distinguished. Below a certain drug load, the limit of drug load, carrier-enabled dissolution occurred, and above this value, the drug defined the dissolution rate. For a carrier-enabled behavior, the dissolution kinetics can be divided into a first fast phase, a second slow phase and a transition phase in between. This study contributes to the understanding of the dissolution mechanism in solid crystalline formulations and is thereby valuable for the process and formulation development. [ABSTRACT FROM AUTHOR]

Purpose: This study was aimed to develop polymeric nanoparticles (PNPs) using chitosan (CTN), polyvinyl pyrrolidone (PVP), and Tween 80 for dissolution enhancement of poorly water-soluble antidiabetic drug: glimeperide (GLM). Methods: GLM-loaded PNPs were developed for increasing the dissolution and solubility of GLM by using different amounts of CTN as polymer, PVP, and Tween 80 as stabilizers and tri-polyphosphate (TPP) as a crosslinking agent. PNPs were prepared using a combined approach of solvent evaporation and ionic gelation techniques. The newly fabricated PNPs were further characterized for percent encapsulation efficiency (%EE), compatibility studies, average particle size, morphology, thermal behavior, XRD examination, and dissolution studies at different biorelevant pH conditions. Results: The prepared PNPs showed % encapsulation efficiency in the range of 55.90 to 93.25%. Fourier transform infrared studies revealed compatibility of GLM with formulation composites. The optimized PNPs F1PVP and F4TW80 showed particle size in nanoscale range 323 nm and 149 nm, respectively. SEM indicated formation of irregular (flakes) shaped particles. DSC and PXRD studies revealed reduction in crystallinity of the GLM inside PNPs thus promoting the dissolution. The dissolution studies at biorelevant acidic pH 1.2 and biorelevant basic pH 6.8 demonstrated remarkable improvement in dissolution profile compared to pure aqueous dispersion of GLM. Conclusion: Overall results of the study suggested that CTN-based PNPs stabilized with PVP and Tween 80 can act as promising carriers for oral drug delivery of GLM. [ABSTRACT FROM AUTHOR]

Background: Abiraterone acetate is an anticancer molecule indicated for prostate cancer. The purpose of this study was to develop a nanosuspension of abiraterone acetate in order to improve its solubility, dissolution properties and bioavailability. Materials and Methods: High speed homogenization method was utilized to formulate the nanosuspension. Design of experiment (DoE) was employed for the optimization of process and formulation variables. Nanosuspension was evaluated for particle size, PDI, zeta potential, and in vitro drug release studies. Results: Preliminary studies suggested amount of stabilizer and milling time as critical variables to be taken for the optimization process. Regression analysis suggested influence of independent variables on responses. Optimized batch obtained from desirability function yielded 140.25 nm of particle size and 0.09 of PDI values. Characterization studies i.e. Differential Scanning Calorimetry and X-Ray Diffraction studies illustrated decrease in crystallinity of drug which might be thereby responsible for the dissolution enhancement of drug. The drug and formulation were found to be stable over a 6-months period in accelerated stability testing. Conclusion: Using high speed homogenization method, particle size of the formulation was reduced to nano-size which was further responsible for the improvement in dissolution and bioavailability of drug. [ABSTRACT FROM AUTHOR]

Abiraterone acetate is a novel antiandrogen drug indicated for prostate cancer. However, it suffers from low bioavailability owing to poor dissolution properties. The present work was aimed to develop abiraterone acetate nano-micelles to improve its dissolution properties and oral bioavailability. Film hydration method was employed to fabricate the abiraterone acetate nano-micelles. Impact of various variables on the formulation of abiraterone acetate nano-micelles were studied in the preliminary trials. Central composite design was employed with independent variables identified in the preliminary studies, viz. X1- Stirring speed and X2- Stirring time. Drug release studies were carried out to check the change in dissolution properties of abiraterone acetate nano-micelles as compared to pure drug. In vivo animal studies were carried out to check the pharmacokinetic parameters. Drug physical alterations caused by nano-micellization were analyzed by solid state characterization (FTIR, DSC, XRD and SEM) experiments. Accelerated stability studies for six months was carried out on the optimized formulation. Results demonstrated influence of various process variables on particle size of abiraterone acetate nano-micelles. In vitro dissolution showed an increase in drug release rate from nano-micelles as compared to pure drug dispersion. Abiraterone acetate nano-micelle's oral bioavailability significantly improved by 32-fold. Accelerated stability studies of the optimized formulation suggested stability of the nano-micelles for at least six-month time. Thus, dissolution properties and oral bioavailability of abiraterone acetate was enhanced by formulating nano-micelles. [ABSTRACT FROM AUTHOR]

Curcumin is a natural polyphenol exhibiting potentials in anti-inflammatory, antioxidant, anti-tumor, and tissue regeneration. Despite its biological significances, the extremely low solubility of curcumin is a serious impediment to its clinical practice. In this study, a curcumin-calcium silicate solid dispersion was prepared via a classical ethanol-based solvent evaporation, in which mesoporous calcium silicate (mesoCS) was applied as dispersion medium aimed to improve water solubility and bioavailability of curcumin. The physicochemical properties of the resulting solid dispersions were characterized by FTIR, XRD, SEM, TEM, DSC, and BET, respectively. In addition, loaded curcumin revealed a curcumin/mesoCS weight ratio depended dissolution improvement and over 60% of curcumin dissolved in the first 5 min for 1/9 weight ratio group. The released curcumin showed a 3410-fold increase of solubility of the original one, accompanied with anti-oxidant activity preservation. These results suggest mesoCS can be a potential solid dispersion carrier for curcumin in oral administration. [ABSTRACT FROM AUTHOR]

The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer. [ABSTRACT FROM AUTHOR]

Glibenclamide (GB), oral antidiabetic sulfonylurea, is used in the management of diabetes mellitus type II. It suffers from low bioavailability due to low water solubility. This work aimed to enhance the dissolution of GB by formulating the drug as a proniosomes which then improves the pharmacological effect. GB proniosomal formulations were prepared using a slurry method with sucrose as a carrier. The formulations were characterized by particle size, zeta potential, entrapment efficiency %, flow properties of the powder, and in vitro dissolution study. The pharmacological effect was also assessed by determining and measuring the fasting blood glucose level (BGL) before and after the treatment. Formulating GB proniosomes with the slurry method produces a free-flowing powder with a particle size range from 190.050 ± 43.204 to 1369.333 ± 150.407 nm and the zeta potential was above 20 mV (-24 to −58 mV), indicating good stability. The dissolution rate for all formulations was higher than that of the pure drug, indicating the efficiency of the proniosome in enhancing the drug solubility. A significant reduction in the fasting blood glucose level (73 %) was observed in animals treated with proniosomal formulation with no sign of liver damage. In contrast, the pharmacodynamics results show a significant reduction in fasting blood glucose level for animals treated with proniosomes compared to a 17.6 % reduction in BGL after treatment with pure drug. Moreover, the histopathological results showed no sign of liver damage that occurred with proniosomal treatment. GB proniosomal formulations is a promising drug delivery system with good therapeutic efficacy and stability.

Purpose: This study aimed to develop niosomes using polyoxyethylene lauryl ether (Brij-35) and poloxamer 407 surfactants for dissolution enhancement of tacrolimus, a poorly water-soluble drug for improving oral bioavailability. Methods: Niosomes were prepared using surfactants polyoxyethylene lauryl ether (Brij-35) (Group I), poloxamer 407 (Group II), and hybrid niosomes including both Brij-35 and poloxamer 407 (Group III). A thin film hydration technique was employed for the development of niosomes. Drug-surfactant interactions were examined using FTIR. The entrapment efficiency of niosomes was determined using ultra-centrifugation technique. Vesicle size, PDI, and zeta potential were measured by DLS experiments. Morphological evaluation of vesicles was carried out using SEM microscopy. DSC technique was used to evaluate the thermal behavior of niosomes. In vitro dissolution study of optimized niosomes (F1-Br35, F1-PL407, and F1-BrPL) was performed by dialysis bag method. Results: FTIR studies revealed the compatibility of tacrolimus with used surfactants. Percent entrapment efficiency values were in the range of 88.65 ± 3.13 to 93.67 ± 1.57% for Brij-35-based formulations, 87.83 ± 6.24 to 89.01 ± 5.83% for poloxamer 407, and 90.08 ± 1.12 to 92.81 ± 0.31% for hybrid niosomes. The vesicle size of niosomes was in the range of 282.5 to 622.5 nm. SEM analysis showed an almost spherical shape of optimized formulations (F1-Br35, F1-PL407, and F1-BrPL). DSC analysis demonstrated amorphous form of tacrolimus indicating improved dissolution of tacrolimus. In vitro dissolution of optimized formulations F1-Br35, F1-PL407, and F1-BrPL at pH 7.4 indicated an improved dissolution profile of tacrolimus compared to pure drug aqueous dispersion. Conclusion: Overall, the results of the study concluded that newly developed niosomes could act as a promising approach for enhancing the dissolution profile of tacrolimus and can act as alternate oral carriers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to improve the solubility and dissolution rate of finasteride (FIN) by searching for an optimal carrier to prepare the FIN carrier solid dispersions (SDs) and to invent a new solvent evaporation instrument for solid dispersion preparation. Methods: The solubility parameter was first used as a criterion to choose out the optimal carriers for FIN SDs, which has wonderful compatibility between the drug and carrier. Different carriers (hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG 4000), and polyethylene oxide N-60 K (PEO)) were selected with different FIN-to-carrier ratios (1:1, 1:2.5, 1:5, 1:7.5, and 1:10, w/w). The FIN SDs were prepared by a new instrument with the cyclone separation principle which is named cyclone-enhanced nitrogen blower. The prepared SDs were then characterized by solubility, DSC, PXRD, FT-IR, dissolution, cumulative dissolution velocity, and stability studies. Results: The results of solubility parameters and kinetic solubility were consistent. All three FIN SDs were successfully synthesized by the new method of nitrogen-blowing solvent evaporation with cyclone enhancement. FT-IR revealed significant intermolecular interactions which are formed by hydrogen bonds between the amide group on ring A of FIN and the hydroxyl group of HPMC. PXRD and DSC analysis indicated that the morphological structure of the FIN was converted into an amorphous or a molecular solution state and lost its original crystallographic structure when FIN was combined with dispersion carriers. The SDs prepared using the new method exhibited good stability, as demonstrated by the stability studies. Furthermore, the FIN-HPMC solid dispersion system in a mass ratio of 1:5 showed the best improvement in solubility and dissolution rate. Conclusions: The solid dispersion system of FIN and HPMC in a mass ratio of 1:5 was the most promising combination to improve dissolution among all tested systems. Moreover, the new instrument of cyclone-enhanced nitrogen blower is an effective and high-throughput way for the preparation of SDs. [ABSTRACT FROM AUTHOR]

Active pharmaceutical ingredients that have low aqueous solubility pose a challenge in the field of drug delivery. In this paper we report for the first time the synthesis of nano-structured, hydrophilized polylactic acid (nf PLA) and its application in the delivery of low solubility drugs. Microwave induced acid oxidation was used to generate nf PLA where the oxygen concentration increased from 27.0 percent to 41.0 percent. Also, the original non dispersible PLA was converted to a relatively dispersible form with an average particle size of 131.4 nm and a zeta potential of -23.3 mV. Small quantities of the nf PLA were incorporated into the crystals (0.5 to 2.0 % by weight) of a highly hydrophobic, low solubility antifungal drug Griseofulvin (GF) to form a composite (GF- nf PLA). An antisolvent approach was used for the synthesis of the drug composite. SEM and Raman imaging showed non-uniform distribution of the nf PLA on the crystal surface. The solubility of GF increased from 8.89 µg/mL to as high as 49.67 µg/mL for the GF- nf PLA. At the same time zeta potential changed from -15.4 mV to -39.0 mV, therefore the latter was a relatively stable colloid. Octanol-water partitioning also showed a similar effect as logP reduced from 2.16 for pure GF to 0.55 for GF- nf PLA. In vitro dissolution testing showed six times higher aqueous solubility of GF- nf PLA compared to pure GF. The time for 50 (T 50) and 80 % (T 80) dissolution reduced significantly for the nf PLA composites; T 50 reduced from 40.0 to 14.0 min and T 80 reduced form unachievable to 47.0 min. Overall, the PLA which is an FDA approved, bioabsorbable polymer can be used to enhance the dissolution of hydrophobic pharmaceuticals and this can lead to higher efficacy and lower the required dosage for drugs. [Display omitted] • Microwave radiation triggered for hydrophilic functionalization of PLA. • Nano functionalized polymer was effectively surface dispersed into griseofulvin. • nf PLA integration had no alternating effect on crystal surface and structure morphology. • Composite drug produced upto 6.0 times increase in aqueous solubility. • Cold antisolvent precipitation technology developed formulated drugs release rates. [ABSTRACT FROM AUTHOR]

Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% w/w. Microfibres were exposed to high relative humidity conditions (25 °C/75% RH) for 30 days to deliberately induce sucrose recrystallisation and collapse of the fibrous structure into powdery particles. The collapsed particles were successfully processed into pharmaceutically acceptable tablets using a dry mixing and direct compression approach. The dissolution advantage of the fresh microfibres was maintained and even enhanced after humidity treatment for drug loadings up to 30% w/w and, importantly, retained after compression into tablets. Variations in excipient content and compression force allowed manipulation of the disintegration rate and drug content of the tablets. This then permitted control of the rate of supersaturation generation, allowing the optimisation of the formulation in terms of its dissolution profile. In conclusion, the microfibre-tablet approach has been shown to be a viable method for formulating poorly soluble BCS Class II drugs with improved dissolution performance. [ABSTRACT FROM AUTHOR]

This study demonstrated the implementation of a liquisolid technique to formulate directly compressible orally disintegrating tablets (ODTs). Cannabidiol (CBD), a hydrophobic cannabinoid, was prepared as a liquisolid powder using microcrystalline cellulose–colloidal silicon dioxide as a carrier–coating material. Different liquid vehicles differing in their volatility, hydrophilicity, and viscosity were investigated. Each of the CBD–ODTs comprised CBD liquisolid powder (10 mg CBD), superdisintegrant, flavors, lubricant, and filler. The physical mixture (PM) ODT was prepared as a control. Ethanol-based ODTs (CBD–EtOH–ODTs) had comparable tablet properties and stability to CBD–PM–ODTs. ODTs with nonvolatile-vehicle-based liquisolid powder had lower friability but longer disintegration times as compared with CBD–PM–ODTs and CBD–EtOH–ODTs. Compression pressure influenced the thickness, hardness, friability, and disintegration of the ODTs. With a suitable compression pressure to yield 31-N-hardness-ODTs and superdisintegrant (4–8%), CBD–ODTs passed the friability test and promptly disintegrated (≤25 s). Times to dissolve 50% of CBD–PM–ODTs, CBD–EtOH–ODTs, and nonvolatile-vehicle-based CBD–ODTs were 10.1 ± 0.7, 3.8 ± 0.2, and 4.2 ± 0.4–5.0 ± 0.1 min, respectively. CBD–EtOH–ODTs exhibited the highest dissolution efficiency of 93.5 ± 2.6%. Long-term and accelerated storage indicated excellent stability in terms of tablet properties and dissolution. Nonvolatile-vehicle-based CBD–ODTs exhibited a higher percentage of remaining CBD. This study provides useful basic information for the development of ODT formulations using a liquisolid technique application. [ABSTRACT FROM AUTHOR]

Naringenin (NAR) is a natural anticancer, but it has not been developed for clinical use despite its therapeutic potential due to its low water solubility, low membrane permeability, first-pass metabolism, and low bioavailability. To overcome these problems, the optimization and preparation of NAR-Soy protein complex (NAR-Sp) led to the optimum ratio of their interaction using Fourier Transform-Infrared spectroscopy (FT-IR) as the first level and layer of the formulation. The second layer of the formulation was to incorporate the NAR-Sp complex in aqueous-based gel-forming. The most optimum nanosuspension was determined using the gel sedimentation, sustained-release, pH-selective and targeted system. The most optimum components combinations and complex were characterized using different characterization tools, such as, the particle size analysis, SEM, TEM, PXRD and FT-IR. In addition, the optimum nanosuspension was characterized for its nanoparticle sensitivity against colorectal cancer cells using MTT assay in comparison to the untreated, naringenin, and blank groups. The complex enhanced the NAR's dissolution. The complex incorporation in the optimum nano-encapsulating system was characterized by the sustained-release and pH-selective behaviors to target the NAR release at the site of action or absorption. Interestingly, the optimum nano-encapsulating system was showing better colorectal cytotoxicity results in comparison to the other groups. [Display omitted] The oral dual-layer system behavior and the gastrointestinal tract media, conditions, and transit time decrease the gastric residency time and increase the intestinal-colonic residency with NAR enhanced dissolution profile using the soy protein complexation. [ABSTRACT FROM AUTHOR]

Lumefantrine, exhibits poor bioavailability due to its very low solubility. A liquisolid compact of lumefantrine was prepared with mesoporous silica as a novel coating material. Lactose anhydrous and syloid 244FP were selected as carrier and coating materials respectively. Varying the carrier to coating ratio from 10 to 35, six formulations were prepared and evaluated for tests for tablets. thermal, surface characteristics, surface morphology, and surface area analysis. The tabletability of the formulation lactose to syloid 244FP ratio at 20:1 was found to be the best among all in terms of compression characteristics, faster disintegration, and enhanced dissolution. Hence it can be concluded that the use of a suitable amount of mesoporous silica in the formulation of liquisolid compact could significantly enhance the dissolution of the drug.

[Display omitted] Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within the pores, improving their dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious synthesis from Si wafer material, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF) and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, −GRI and −DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability. [ABSTRACT FROM AUTHOR]

Telmisartan is a poorly water-soluble drug with dissolution limited bioavailability. In this work, solubility and dissolution rate were aimed to improve through the development of cyclodextrin (CD) complexes containing surfactant; followed by developing them into orodispersible tablets (ODTs). Quality by design approach was adopted in the optimization of CD-surfactant complex as well as in the optimization of ODTs. Type of cyclodextrins, the concentration of the cyclodextrins, and concentration of poloxamer 188 were taken as the factors in the preparation of inclusion complexes by solvent evaporation method. Solubility was taken as the response variable. The optimized formulation of the complex was taken for ODTs preparation. Concentration of povidone, concentration of super-disintegrant and type of super-disintegrant were taken as the independent factors, and disintegration time (DT) and time for 90% dissolution (T90%) were taken as the responses. The tablets were prepared by direct compression technique. The results of both the responses were analyzed by response surface quadratic model for the influence of the factors on them. All three factors were found to have significant influence on both the responses (at p < 0.05). Graphical optimization was performed by desirability functions approach in order to have low DT and low T90%. The optimized telmisartan CD-surfactant complex was found to have a solubility of 2.86 mg/mL. The optimized ODTs were found to have 20.4 sec. DT and 7.3 min. T90%. These results indicated that enhancement of solubility of telmisartan as well as dissolution of the ODTs was successfully improved through quality by design approach. [ABSTRACT FROM AUTHOR]

Purpose: Liqui-Tablet is a dosage form derived from Liqui-Mass technology. It has proven to be a promising approach to improve drug dissolution rate of poorly water-soluble drugs. So far, Liqui-Tablet is feasible for low-dose drugs. In this study, an attempt was made to produce high-dose Liqui-Tablet, whilst maintaining ideal physicochemical properties for ease of manufacturing. Methods: Liqui-Tablets containing 100 mg of ketoprofen were produced using various liquid vehicles including PEG 200, Span 80, Kolliphor EL, PG, and Tween 85. Investigations that were carried out included saturation solubility test, dissolution test, tomographic study, and typical quality control tests for assessing flowability, particle size distribution, friability, and tablet hardness. Results: The weight of these Liqui-Tablets was acceptable for swallowing (483.8 mg), and the saturation solubility test showed PEG 200 to be the most suitable liquid vehicle (493 mg/mL). Tests investigating physicochemical properties such as flowability, particle size distribution, friability, and tablet hardness have shown no issue concerning quality control and manufacturability. The drug release test of the best formulation has shown extremely rapid drug release at pH 7.4 (100% after 5 min). At pH 1.2 the drug release was reasonable considering the formulation was yet to be optimized. Conclusion: Despite the high amount of API and liquid vehicle, it is possible to produce a high-dose dosage form with acceptable size and weight for swallowing using the novel Liqui-Mass technology. This has the potential to diversify the technology by removing the restriction of high dose drug that has been seen in liquisolid technology. [ABSTRACT FROM AUTHOR]

The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3rd generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m2/g and 8.2757 m2/g, respectively. [ABSTRACT FROM AUTHOR]

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine. [ABSTRACT FROM AUTHOR]

The advantage of nanoparticles to improve bioavailability of poorly soluble drugs is well known. However, the higher-energy state of nanoparticles beneficial for bioavailability presents challenges for both the stability of nanosuspensions and preventing irreversible aggregation if isolated as dry solids. The aim of this study is to explore the feasibility of an evaporation isolation route for converting wet media milled nanosuspensions into high drug-loaded nanocomposites that exhibit fast redispersion in aqueous media, ideally fully restoring the particle size distribution of the starting suspension. Optimization of this approach is presented, starting from nanomilling conditions and formulation composition to achieve physical stability post milling, followed by novel evaporative drying conditions coupled with various dispersant types/loadings. Ultimately, isolated nanocomposite particles reaching 55–75% drug load were achieved, which delivered fast redispersion and immediate release of nanoparticles when the rotary evaporator drying approach was coupled with higher concentration of hydrophilic polymers/excipients. This bench-scale rotary evaporation approach serves to identify optimal nanoparticle compositions and has a line of sight to larger scale evaporative isolation processes for preparation of solid nanocomposites particles. [ABSTRACT FROM AUTHOR]

The objective of the present investigation was to develop and optimize spray dried solid dispersion for dissolution enhancement of an anti-HIV drug, Nevirapine. The pareto chart of Plackett and Burman screening design revealed that drug: polymer ratio, concentration of silicon dioxide, and feed flow rate had a significant effect on production yield and drug release (Q60). These factors were further studied using central composite design to obtain optimized formulation. Optimized formulation was characterized by DSC, XRD, and SEM, and studied for drug release and accelerated stability. Spray dried solid dispersion formulated with drug: polymer ratio of 1:2, 2% w/w silicon dioxide and 1 mL/min flow rate gave the best result of 69.02% production yield and 80.46% drug release. [ABSTRACT FROM AUTHOR]

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds’ increase in dissolution rate compared to pure TDL. The results obtained from the in vivo study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

[Display omitted] • Celecoxib (CLX) as a low water-soluble drug has a limited bioavailability. • Supercritical CO 2 as an anti-solvent crystallization (SAS) were applied. • Box-Behnken design was used to optimize the effect parameters of the SAS. • The optimal SAS sample increased the solubility and dissolution rate of CLX. • The SAS produced the sponge like particles with decreased crystallinity. For dissolution enhancement of celecoxib (CLX), an anti-solvent crystallization technique in the presence of polyvinylpyrrolidone (PVP) was applied by either water (WAS), a conventional method, or supercritical CO 2 as anti-solvent (SAS). Box-Behnken design with the parameters of temperature (T), pressure (P), and time required to depressurize (t d) was applied to examine the effect of variables in the SAS process. In the SAS process, maximum dissolution (81.7 % after 90 min) and saturation solubility (8.6 μg/mL) were obtained when the T, P, and t d were 50 °C, 300 bar, and 20 min, respectively. Optimal SAS samples exhibited a higher dissolution rate compared to particles obtained by the WAS. The presence of PVP in the SAS sample increased the solubility of CLX by 2.7-fold in comparison to untreated CLX. The greater dissolution rate of the SAS sample could arise from the formation of sponge-like particles with increased porosity, crystallinity reduction, and increased CLX solubility. [ABSTRACT FROM AUTHOR]

This study sought to investigate the influence of formulation and process factors of the high shear mixing (HSM) on the properties of solid self-emulsifying drug delivery systems (S-SEDDS) containing the model drug carvedilol (CAR). Firstly, liquid SEDDS (L-SEDDS) were prepared by mixing castor oil with different proportions of surfactant (Solutol or Kolliphor RH40) and cosolvent (Transcutol or PEG400). A miscible L-SEDDS with high drug solubility (124.3 mg/g) was selected and gave rise to 10% (m/m) CAR loaded-emulsion with reduced particle size. Then, a factorial experimental design involving five component's concentration and two process factors was used to study the solidification of the selected L-SEDDS by HSM. CAR content, diffractometric profile, and in vitro dissolution were determined. Morphological and flow analyses were also performed. Porous and spherical particles with mean sizes ranging from 160 to 210 µm were obtained. Particle size was not affected by any formulation factor studied. Powder flowability, in turn, was influenced by L-SEDDS and crospovidone concentration. CAR in vitro dissolution from S-SEDDS was significantly increased compared to the drug as supplied and was equal (pH 1.2) or lower (pH 6.8) than that determined for L-SEDDS. Colloidal silicon dioxide decreased drug dissolution, whereas an increase in water-soluble diluent lactose and L-SEDDS concentration increased CAR dissolution. The proper selection of liquid and solid constituents proved to be crucial to developing an S-SEDDS by HSM. Indeed, the results obtained here using experimental design contribute to the production of S-SEDDS using an industrially viable process. [ABSTRACT FROM AUTHOR]