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The current state of drug delivery systems allows for the resolution of specific issues like inadequate solubility, limited targeting capabilities, and complex preparation processes, requiring tailored designs for different drugs. Yet, the major challenge in clinical application lies in surmounting these obstacles with a universal carrier that is effective for a variety of anticancer drugs. Herein, with the help of computer simulation, we rationally design ultrashort peptides GY and CCYRGD, which can co-assemble with hydrophobic anticancer drugs into nanoparticles with enhanced solubility, targeting ability and anticancer efficacy. Taking 7-ethyl-10-hydroxy camptothecin (SN38) as a model anticancer drug, the co-assembled SN38-GY-CCYRGD nanoparticles significantly enhance the water solubility of SN38 by more than three orders of magnitude. The as-prepared nanoparticles can effectively kill cancer cells, e.g., human small cell lung cancer (A549) cells with a notable cell mortality rate of 71%. Mice experimental results demonstrate the nanoparticles' efficient targeting capability, marked reducing the toxicity to normal tissues while improving antitumor efficacy. This work presents a novel drug delivery method, integrating effective, targeted, and safe strategies into a comprehensive carrier system, designed for the administration of hydrophobic anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has multi-disciplinary applications spanning across the development of drug delivery systems, in 3D printing, and in tissue engineering, etc. HPMCAS helps in maintaining the drug in a super-saturated condition by inhibiting its precipitation, thereby increasing the rate and extent of dissolution in the aqueous media. HPMCAS has several distinctive characteristics, such as being amphiphilic in nature, having an ionization pH, and a succinyl and acetyl substitution ratio, all of which are beneficial while developing formulations. This review provides insights regarding the various types of formulations being developed using HPMCAS, including amorphous solid dispersion (ASD), amorphous nanoparticles, dry coating, and 3D printing, along with their applicability in drug delivery and biomedical fields. Furthermore, HPMCAS, compared with other carbohydrate polymers, shows several benefits in drug delivery, including proficiency in imparting stable ASD with a high dissolution rate, being easily processable, and enhancing bioavailability. The various commercially available formulations, regulatory considerations, and key patents containing the HPMCAS have been discussed in this review., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The study was designed to prepare pure curcumin nanoparticles in rapid and simple way for target specific drug delivery to kill bacteria lying deep down within the alveoli of lungs via inhaler. Three different methods including evaporation precipitation of nanosuspension (ENP), solid dispersion (SD) and anti-solvent precipitation (ASP) were selected to prepare nanocurcumin in pure form in very simple way. This was done to compare their efficiency in terms of particle size obtained and water solubility and bacterial toxicity of as prepared curcumin nanoparticles. In this comparative study, curcumin NPs obtained from three different methods having particles size 65.3 nm, 98.7 nm and 47.4 nm respectively. The NPs were characterized using various techniques like SEM, XRD, UV-Visible and FTIR for their particle size determination and solubility evaluation. These particles were screened off against five bacterial strains causing lung diseases. AB 3 prepared by ASP method, being smallest sized nanostructures, showed maximum solubility in water. These nanoparticles can be used as drug directly via inhaler to the target area without using any support or nano-carrier. In this way minimum dose formulation is required to target bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Iloperidone (IP) is an antipsychotic drug which belongs to Biopharmaceutical Classification System (BCS) II exhibiting poor aqueous solubility. The current investigation explores the possibility of enhancement of solubility and dissolution characteristics of IP by formulation of liquid self-nano emulsifying drug delivery system (L-SNEDDS) utilizing Box-Behnken Design (BBD) and desirability function., Methods: The oils, surfactants and co-surfactants used in the study were selected based on solubility of the drug and their emulsification ability. Optimization of the formulation was performed using BBD by employing four response variables such as globule size (nm), percentage transmittance (%), self-emulsification time (sec) and percent drug released in 15min. 2D contour plots and 3D response surface plots were constructed using Design Expert software., Results: The developed optimal L-SNEDDS of IP through BBD approach resulted in improvement of solubility and dissolution rate as compared with the pure drug. Based on desirability function, optimized formulation was prepared and was assessed for response variables (globule size, percentage transmittance, self-emulsification time and percent drug dissolved in 15min). The characterization studies revealed droplet size to be 21.80±2.41nm, 99.584±0.65% transmittance, 24.43±2.12sec emulsification time and 95.31±1.57% cumulative drug release in 15min., Conclusion: The results conclude the potentiality of prepared L-SNEDDS in improving solubility and dissolution rate of IP., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

In this paper, we propose a facile program of preparing nanoscale γ-cyclodextrin-based metal-organic frameworks (Nano-CD-MOFs) for the encapsulation of curcumin. Such Nano-CD-MOFs not only possess excellent mono-dispersity and crystalline structure, but also perform superior loading capacity. The results of N 2 adsorption-desorption, XRD, DSC, and microtopography are utilized to confirm the presence status of encapsulated curcumin and further reveal the encapsulation mechanism of Nano-CD-MOFs. Curcumin-loaded Nano-CD-MOFs (Cur-Nano-CD-MOFs) dramatically increase curcumin solubility and a top-down uniform dispersion in the dissolution process. The perfect fitting of First-order and Korsmeyer-Peppas models suggests that the release performance of Nano-CD-MOFs is controlled by the loaded quantity of curcumin and related to Fickian diffusion. Moreover, the antioxidative stability of Cur-Nano-CD-MOFs is considerably enhanced even after 120 min of persistent ultraviolet irradiation. Therefore, we suggest that such Nano-CD-MOFs can be promoted as an advanced carrier for the delivery of curcumin or other nutraceuticals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The present study focused on establishing a novel, (pre-)screening approach that enables the development of promising performing self-nanoemulsifying drug delivery systems (SNEDDSs) with a limited number of experiments. The strategic approach was based on first identifying appropriate excipients (oils/lipids, surfactants, and co-solvents) providing a high saturation solubility for lipophilic model compounds with poor aqueous solubility. Excipients meeting these requirements were selected for SNEDDS development, and a special triangular mixture design was applied for determining excipient ratios for the SNEDDS formulations. Celecoxib and fenofibrate were used as model drugs. Formulations were studied applying a specific combination of in vitro characterization methods. Specifications for a promising SNEDDS formulation were self-imposed: a very small droplet size (< 50 nm), a narrow size distribution of these droplets (PDI < 0.15) and a high transmittance following SNEDDS dispersion in water (> 99% in comparison with purified water). Excipients that provided a nanoemulsion after dispersion were combined, and ratios were optimized using a customized mapping method in a triangular mixture design. The best performing formulations were finally studied for their in vitro release performance. Results of the study demonstrate the efficiency of the customized screening tool approach. Since it enables successful SNEDDS development in a short time with manageable resources, this novel screening tool approach could play an important role in future SNEDDS development. Graphical abstract., (© 2021. The Author(s).)

Atopic dermatitis (AD) is a repetitive inflammatory skin disorder with limited treatment options. Innovative targeted therapies are gaining significant interest and momentum towards disease control including better ways to deliver drugs topically. Tacrolimus is one such compound which is used to manage moderate to severe AD without causing atrophy which is one of the common side effects of steroids. However, Tacrolimus suffers from poor solubility and retention in the skin when used alone in hydrogel. Therefore, we have prepared Tacrolimus loaded mesoporous silica nanoparticles (TMSNs) to overcome the issues related to its solubility and effective topical delivery. Mesoporous silica nanoparticles (MSNs) were synthesized using sol gel technique and surface functionalized using amino (-NH 2 + ) and phosphonate (-PO 3 - ) groups. Tacrolimus was loaded into MSNs and the particles were characterized for particle size (TEM and DLS), zeta potential (DLS), solubility studies, FTIR, TGA, XRD, BET and cytotoxicity studies. Water solubility of Tacrolimus was increased by 7 folds with phosphonate functionalized MSNs compared to free Tacrolimus. Further the TMSNs were incorporated in to carbopol gel, and the gel formulation was evaluated for various gel characterization tests (pH, spreadability, viscosity), in vitro tests (drug release, permeability studies) and in vivo tests (skin irritation study and efficacy studies) using 1-Fluoro-2,4-dinitrobenzene (DNFB) induced dermatitis in Balb/c mice. Results of in vitro and in vivo study showed that TMSNs loaded gel showed significantly higher amount of Tacrolimus retained (ex vivo - rat skin) and much higher reduction in ear thickness and improved histology (in vivo - in mice). Our data collectively suggest that MSNs incorporated hydrogel as a promising new formulation strategy for topical delivery of poorly soluble drugs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Poor bioavailability and solubility of drugs in aqueous phase are the most important problems of newly developed chemical entities that can be improved by nanoemulsion., Objectives: BCS class II and IV which are poorly soluble in water demonstrate various problems in conventional dosage forms. For the improvement of solubility, bioavailability and getting the best therapeutic effect of poorly soluble drugs nanoemulsion is the best solution., Methods: Nanoemulsion are thermodynamically unstable isotropic system with droplet size 1-100 nm in which two immiscible fluids are combined together to form one phase by using an emulsifying agent. Nanoemulsion can be designed to promote the bioavailability of API by trapping them inside., Results: Nanoemulsion can be developed in many dosage forms such as oral, parenteral, topical, ophthalmic dosage form in large scale using common operation at a very low cost. Large range of lipophilic drugs can be easily incorporated in nanoemulsion., Conclusion: In this review, attention is focused on the type of nanoemulsions, their advantages over other dosage form, method for their preparation, characterization, applications and patents in various fields., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Poor aqueous solubility is currently a prevalent issue in the development of small molecule pharmaceuticals. Several methods are possible for improving the solubility, dissolution rate and bioavailability of Biopharmaceutics Classification System (BCS) class II and class IV drugs. Two solid state approaches, which rely on reductions in order, and can theoretically be applied to all molecules without any specific chemical prerequisites (compared with e.g. ionizable or co-former groups, or sufficient lipophilicity), are the use of the amorphous form and nanocrystals. Research involving these two approaches is relatively extensive and commercial products are now available based on these technologies. Nevertheless, their formulation remains more challenging than with conventional dosage forms. This article describes these two technologies from both theoretical and practical perspectives by briefly discussing the physicochemical backgrounds behind these approaches, as well as the resulting practical implications, both positive and negative. Case studies demonstrating the benefits and challenges of these two techniques are presented., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Most drugs used in therapy have low water-solubility, a factor that could reduce their dissolution rate and oral bioavailability, representing a challenge in pharmaceutical development. Nanonization of drugs is the reduction of particles to nanoscale, increasing the surface area and consequently the saturation solubility and dissolution rate and resulting in higher bioavailability., Areas Covered: This review provides an overview of the consequences of the poor water-solubility and the main strategies applied to increase the solubility of poorly water-soluble drugs. The relationship between the biopharmaceutical classification system and the solubilization process of the drug is also considered. Finally, it includes how drug nanoparticles and nanocarriers, especially lipid-based nanosystems, can overcome these challenges and which of these approaches are already available on the market., Expert Opinion: Due to the growing importance of nanomedicines, especially for applications in poorly water-soluble drugs, it is important to clearly establish the specifications and quality criteria for nanonized drugs to ensure the quality and safety of nanoparticles.

Purpose: Etodolac (ETD) is one of the non-steroidal anti-inflammatory drugs which has low aqueous solubility issues. The objective of this study was to develop ETD nanosuspensions to improve its poor aqueous solubility properties while investigating formulation and process parameters of wet media milling method via design of experiment (DoE) approach., Methods: The critical formulation parameters (CFP) were selected as ETD amount, stabilizer type and ratio as well as critical process parameters (CPP) which were bead size, milling time and milling speed. The two-factorial-2 3 and The Box-Benkhen Designs were generated to evaluate CFP and CPP, respectively. Particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were analyzed as dependent variables. Characterization, physical stability and solubility studies were performed., Results: Optimum nanosuspensions stabilized by PVP K30 and Poloxamer 188 showed 188.5 ± 1.6 and 279.3 ± 6.1 nm of PS, 0.161 ± 0.049 and 0.345 ± 0.007 PDI, 14.8 ± 0.3 and 16.5 ± 0.4 mV of ZP values, respectively. The thermal properties of ETD did not change after milling and lyophilization process regarding to DSC analysis. Also, the crystalline state of ETD was preserved. The morphology of particle was smooth and spherical on SEM. The dry-nanosuspensions stayed physically stable for six months at room temperature. The solubility of nanosuspensions increased up to 13.0-fold in comparison with micronized ETD., Conclusions: In conclusion, it is found that the poor solubility issue of ETD can be solved by nanosuspension. DoE approach provided benefits such as reducing number of experiments, saving time and improving final product quality by using wet media milling.

Inflammatory bowel disease (IBD) is a debilitating condition characterized by chronic inflammation of the colon which can increase the risk of colon cancer. Celecoxib (CXB), a cyclooxygenase-2 inhibitor, showed potential for the prophylaxis against IBD. However, it suffers from poor aqueous solubility and cardiovascular toxicity on prolonged use. Here, CXB solubility was enhanced using nanomixed micelles (NMMs) and then colon targeted in a pulsatile system to minimize systemic side effects. Pluronic P123 NMMs with bile salts or hydrophilic Pluronics were prepared using the thin film hydration technique. NMMs were characterized for particle size, size distribution and zeta potential before and after freeze drying and for solubility enhancement. The freeze dried NMMs were then loaded in pulsatile systems with varying tablet plugs containing time-dependent polymers at different concentrations. The optimum NMM consisted of Pluronic P123 and sodium taurocholate (1:1) and CXB:surfactant mixture ratio of 1:30. The pulsatile capsules, containing a tablet plug made of 75% Carbopol®, achieved the target release profile with 88.35% of the dose released after an 8 hrs lag period. Finally, the optimum NMM/pulsatile system showed protective effect against experimentally-induced colitis compared to conventional capsules and pulsatile capsules filled with pure CXB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

While the solubility enhancement capability of amorphous drug-polyelectrolyte nanoparticle complex (nanoplex) has been widely established, its amorphous form stability during long-term storage is often lacking for poorly-soluble drugs with high crystallization propensity, such as curcumin (CUR). Herein we presented a new stabilization strategy of amorphous CUR nanoplex using a secondary small-molecule drug - ibuprofen (IBU) - as the auxiliary stabilizer to the polyelectrolytes (i.e. chitosan). The results showed that, unlike the single-drug CUR nanoplex, the dual-drug CUR-IBU nanoplex with CUR/IBU payload ratio of 1.7 remained stable after 24-month storage. The CUR-IBU nanoplex also exhibited superior CUR solubility enhancement (4-fold higher) than the CUR nanoplex. These improvements, however, were not evident for the CUR-IBU nanoplex prepared at higher CUR/IBU payload ratio of 14 due to insufficient IBU presence. Compared to the CUR nanoplex, the CUR-IBU nanoplex exhibited smaller size with less spherical morphology (100 nm), higher zeta potential (42 versus 19 mV), lower total drug payload (73% versus 83%), and lower CUR utilization rate (53% versus 94%) due to the competition with IBU in the drug-PE complexation. These results successfully established the use of a secondary drug to not only stabilized, but also improved solubility enhancement of amorphous drug nanoplex systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Glabridin, a compound in the root extract of Glycyrrhiza glabra, has been identified as an effective tyrosinase inhibitor. Applied on skin, melanin synthesis is inhibited, making glabridin an interesting candidate for skin whitening or for the treatment of age spots. However, main obstaclefor its practical use is its low dermal bioavailability, caused by its poor water solubility. In this work smartPearls technology was used to increase the glabridins water solubility. smartPearls consist of silica particles with mesopores in which actives can be loaded. By this, actives are stabilized in amorphous state and simultaneously finely distributed in nm-range. Both amorphization and nanoization are well known approaches to increase saturation solubilities. In smartPearls these approaches are combined. In the first step, glabridin smartPearls formulation was developed, screening systematically the suitability of 4 different silicas varying in their pore sizes (3, 6, 10, 17 nm). Also, most suited filling level of glabridin was determined (25, 50, 80% referred to total pore volume of respective silica). Silica loading was performed by the immersion-evaporation method, resulting in pores filled with glabridin from bottom to top. By light microscopy, dynamic scanning calorimetry and X-ray diffraction the sample with 6 nm pore size and filling levels of 25% and 50% have been verified to be completely amorphous. Highest physical storage stability of 7 months up to now was obtained for the 25% filled sample. In the next step, concept of increased saturation solubility for smartPearls was proven. Dissolution profiles were recorded in situ for glabridin smartPearls and compared to glabridin raw drug powder. Both saturation solubility and dissolution velocity were remarkably improved. The water solubility for example increased by a factor of more than 4. This makes glabridin smartPearls promising for creating skin products with improved dermal bioavailability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent analysis of the published data reveals the increasing importance of nanotechnology in the field of drug delivery, especially due to easy modulation of drug release and targeting effect. Various conventional methods including nanoprecipitation, spray drying, solvent evaporation, supercritical fluid extraction and ionotropic gelation are well-explored for lab-scale production of nanoparticles and present their own advantages and limitations. Electrospraying a variant of electrospinning is a method based on the processing of polymeric solutions/melt under high electrical voltage to produce particles of desired nature; post optimization of process parameters. This technique is comparatively newer one presenting itself as a competent alternative for the production of polymeric nanoparticles. Owing to its simplicity and flexibility electrospraying can be used to generate particulate material with meticulous structure, size and morphology; providing advantages of controlled release, improved dissolution rate, taste masking of drug candidates and many more. There is very less literature offering pertinent information about the production of nanoparticles by electrospraying technique as most of them deal with materialistic parameters only. This creates a void in learning and understanding of this novel technique for production of nanoparticles encapsulating drug candidates. Also there is a need of exploration in terms of drug release. Present article will provide an overview of electrospraying based production of nanoparticles for controlled and customized drug delivery, to fill this gap. Basic principle, instrumental set-up, advantages and limitations of electrospraying technique over other conventional nanoparticle production techniques and critical process parameters affecting nanoparticle properties is dealt in detail. Brief description of various polymeric nanoparticles (Polymers of natural as well as synthetic origin) with numerous case studies is given providing vast knowledge of drug encapsulation and modulated release patterns in correlation to polymer type used, structure and morphology of nanoparticles produced., (Copyright © 2018. Published by Elsevier B.V.)

We report the development of a new spray-drying and nanoparticle assembly process (SNAP) that enables the formation of stable, yet rapidly dissolving, sub-200 nm nanocrystalline particles within a high T g glassy matrix. SNAP expands the class of drugs that spray-dried dispersion (SDD) processing can address to encompass highly crystalline, but modestly hydrophobic, drugs that are difficult to process by conventional SDD. The process integrates rapid precipitation and spray-drying within a custom designed nozzle to produce high supersaturations and precipitation of the drug and high T g glassy polymer. Keeping the time between precipitation and drying to tens of milliseconds allows for kinetic trapping of drug nanocrystals in the polymer matrix. Powder X-ray diffraction, solid state 2D NMR, and SEM imaging shows that adding an amphiphilic block copolymer (BCP) to the solvent gives essentially complete crystallization of the active pharmaceutical ingredient (API) with sub-200 nm domains. In contrast, the absence of the block copolymer results in the API being partially dispersed in the matrix as an amorphous phase, which can be sensitive to changes in bioavailability over time. Quantification of the API-excipient interactions by 2D 13 C- 1 H NMR correlation spectroscopy shows that the mechanism of enhanced nanocrystal formation is not due to interactions between the drug and the BCP, but rather the BCP masks interactions between the drug and hydrophobic regions of the matrix polymers. BCP-facilitated SNAP samples show improved stability during aging studies and rapid dissolution and release of API in vitro.

Raloxifene HCl (RH) has poor water solubility and due to its extensive first pass metabolism; its bioavailability is only 2%. The purpose of the present study was to enhance the aqueous solubility, oral bioavailability and anti-osteoporotic effects of RH by electro-sprayed nanoparticles (NPs) in ovariectomized rats. NPs containing RH and different ratio of poly(methyl vinyl ether-co-maleic acid) (PMVEMA) were electrosprayed. The voltage, distance of needle to the collector, flow rate of the solution and polymeric percentage were optimized according to the size of NPs and drug solubility. The optimized formulation was characterized by SEM, XRD, DSC, and FTIR. The pharmacokinetic parameters were studies by oral administration of a single dose of 15mg/kg in Wistar rats. The anti-osteoporotic effects were studied in female ovariectomized rats. Animals were treated with 6mg/kg/day for 2months then serum calcium, phosphorous and alkaline phosphatase levels were measured. RH loaded electrosprayed NPs showed 10-fold enhanced solubility compared to the free drug. Moreover, the XRD and SEM tests displayed an amorphous state of drug in the NPs. FTIR and DSC tests revealed no interaction between the polymer and the drug. Serum calcium, phosphorous and alkaline phosphatase levels were significantly decreased in ovariectomized rats receiving oral RH NPs (P<0.05). No significant difference was detected between RH NPs and estradiol groups (P>0.05). Oral bioavailability of NPs showed 7.5-fold increase compared to the pure drug. The electrosprayed PMVEMA nanoparticles can enhance solubility, bioavailability and antiosteoporotic effects of RH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Pharmacokinetic issues and poor solubility in water are the most important concerns of numerous recently developed chemical entities., Objective: The drugs which are poorly soluble in water demonstrate numerous formulating troubles in conventional dosage forms and the low bio-availability is the critical problem linked with it. A nanosponge is an emerging technology which can overcome these problems and precisely control the release rates of controlled drug delivery., Method: Nanosponges are tiny mesh-like structures with a size less than 1μm. Due to their porous structure and small size; they can easily bind to drugs which are poorly-soluble leading to better bioavailability and solubility of such drugs. A broad range of drugs including both hydrophilic and lipophilic can be easily loaded into nanosponges., Results: These minute sponges can circulate until they reach the definite target site, attach themselves to the surface and initiate the discharge of drugs in a predictable and controlled way. Nanosponges are solid in character and can be developed in various dosage forms such as parenteral, topical, oral or inhalational. Nanosponge drug delivery system has been developed as one of the most capable aspects in the field of pharmaceuticals., Conclusion: In this review, an attempt has been made to highlight the advantages, characteristics, application, methods of preparation and characterization of nanosponges along with the recent patents on nanosponges., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The solubility enhancement afforded by amorphous drug nanoparticles was demonstrated in several studies to be superior to the traditional amorphization approach by microscale amorphous solid dispersion (or micro ASD in short). A closer look at these studies, however, revealed that they were performed using a very limited number of poorly-soluble drug models (i.e. itraconazole and cefuroxime). Herein we aimed to re-examine the solubility enhancement and physical stability of amorphous nanoparticles relative to that of the micro ASD using a different poorly-soluble drug model, i.e. ciprofloxacin (CIP). Two types of amorphous CIP nanoparticles, i.e. CIP nanorod prepared by pH-shift precipitation and CIP nanoplex prepared by drug-polyelectrolyte complexation, were compared with CIP micro ASD prepared by spray drying with hydroxypropylmethylcellulose (HPMC). The results showed that (1) the solubility enhancement of amorphous drug nanoparticles was not necessarily superior to that of the micro ASD, particularly in their dry-powder form, and (2) the amorphization strategy of drug nanoparticles significantly influenced their solubility enhancement and physical stability. In short, the solubility enhancement was in the order of CIP micro ASD>CIP nanorod>CIP nanoplex, whereas the amorphous state stability during storage was in the order of CIP nanoplex>CIP micro ASD>CIP nanorod. A trade-off thus existed between the solubility enhancement and physical stability of amorphous CIP particles. The present work concluded that the superior solubility enhancement of amorphous drug nanoparticles was not drug independent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pyridoclax is an original oligopyridine lead, very promising in treatment of chemoresistant cancers. However, from solubility measurement and permeability evaluation, it appeared that this compound can be considered as a BCS II drug, with a poor water solubility. To overcome this unfavorable property, two strategies were proposed and compared: pyridoclax di-hydrochloride salt synthesis and formulation of pyridoclax-loaded nanoemulsions (PNEs) efficiently performed by transposing the spontaneous emulsification process previously developed by our team. Whereas the salt improved the thermodynamic solubility of the drug by a factor 4, the apparent solubility of the encapsulated pyridoclax was 1000-fold higher. Their stability was assessed upon dilution in various complex biomimetic media relevant for oral administration (SGF, FaSSIF-V2, FeSSIF-V2) or for the intravenous route (PBS). The solubility of the salt was affected by the nature of the medium, indicating that it could precipitate after administration, negatively impacting its bioavailability and its efficiency in vivo. On the contrary, in all media, PNEs remained stable in terms of granulometric properties (determined by DLS), ζ-potential and encapsulation efficiency (measured by HPLC). Thus, such nanomedicines appear as a valuable option to perform preclinical studies on the promising pyridoclax., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Efavirenz is a non-nucleoside reverse transcriptase inhibitor, and is classified as BCS Class II API. Its erratic oral absorption and poor bioavailability make it a potential candidate for being formulated as a nanosuspension. The objective of this study was to formulate efavirenz nanosuspensions employing the antisolvent precipitation-ultrasonication method, and to enhance its solubility by reducing particle size to the nanometer range. The effects of different process parameters were studied and optimized with respect to particle size and poly dispersity index (PDI). The optimized formulation was also subjected to lyophilization, to further increase the solubility and stability, and the technology is potentially suited to a range of poorly water-soluble compounds.

Resveratrol, a naturally occurring polyphenol and phytoalexin, has received significant attention in recent years due to its vast therapeutic effects including anticancer, antioxidant and anti-inflammatory effects. However, poor pharmacokinetic properties such as low aqueous solubility, low photostability and extensive first pass metabolism result in poor bioavailability, hindering its immense potential. Conventional dosage forms such as dry powder capsules and injections have met with limited success, demonstrating challenges faced in developing an effective formulation. Recently, nanotechnology-based formulations (nanoformulations) are being looked upon as a novel method for improving the pharmacokinetic properties, as well as enhancing targetability and bioavailability of resveratrol. This review outlines the therapeutic potential of resveratrol, explores its mechanisms of action and pharmacokinetic limitations, and discusses the success and challenges of resveratrol-encapsulated nanoparticles in the last decade. Potential techniques to improve encapsulation of the drug within nanoparticles, thereby enhancing its clinical potential are highlighted., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products., Areas Covered: This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported., Expert Opinion: Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.

In this study, Felodipine-loaded nanoparticles were prepared using the nanoprecipitation method, with quince seed mucilage serving as the polymer matrix and Tween 80 utilized as a stabilizing agent. The nanoparticles were thoroughly characterized using a range of analytical techniques, including dynamic light scattering (DLS), zeta potential measurement, Fourier-transform infrared spectroscopy (FTIR), thermal analysis, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The Felodipine nanoparticles displayed an amorphous structure, with formulation FEL 4 achieving the highest entrapment efficiency of 67.68%. This formulation also had an average particle size of 675 ± 2.04 nm and a zeta potential of − 31.7 ± 1.34 mV. Saturation solubility tests revealed a significant enhancement in water solubility for the nanoparticles compared to pure Felodipine. Additionally, in vitro drug release studies demonstrated a sustained release profile over 24 h in phosphate buffer. Acute oral toxicity evaluations confirmed that the Felodipine nanoparticles did not exhibit any signs of toxicity. Overall, this study showed the successful fabrication of quince seed mucilage-based Felodipine-loaded nanoparticles as a promising approach to enhance solubility and achieve sustained drug release, with no evident toxicity. [ABSTRACT FROM AUTHOR]

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described. [ABSTRACT FROM AUTHOR]

Transglycosylation has been used to modify the physicochemical properties of original compounds. As a result, transglycosylated compounds can form molecular aggregates in size ranges of a few nanometers in an aqueous medium when their concentrations exceed a specific level. Incorporating these hydrophobic compounds has been observed to enhance the solubility of hydrophobic compounds into aggregate structures. Thus, this review introduces four transglycosylated compounds as food additives that can enhance the solubility and oral absorption of hydrophobic compounds. Here, transglycosylated hesperidin, transglycosylated rutin, transglycosylated naringin, and transglycosylated stevia are the focus as representative substances. Significantly, we observed that amorphous formations containing hydrophobic compounds with transglycosylated compounds improved solubility and oral absorption compared to untreated hydrophobic compounds. Moreover, combining transglycosylated compounds with hydrophilic polymers or surfactants enhanced the solubilizing effects on hydrophobic compounds. Furthermore, the enhanced solubility of hydrophobic compounds improved their oral absorption. Transglycosylated compounds also influenced nanoparticle preparation of hydrophobic compounds as a dispersant. This study demonstrated the benefits of transglycosylated compounds in developing supplements and nutraceuticals of hydrophobic compounds with poor aqueous solubility. [ABSTRACT FROM AUTHOR]

The formulation of poorly soluble drugs is one of the most difficult tasks for pharmaceutical formulators. Conventional techniques for increasing the solubility of these drugs have had limited success. This is especially true when dealing with drugs that have low aqueous and organic solubility. Solubility is an important determinant of drug liberation and thus drug absorption, and it plays an important role in formulation oral bioavailability. A drug solubility directly influences its dissolution rate. Most New drugs have low water solubility, making them difficult to formulate into drug delivery systems. As a result, improving the solubility of poorly water soluble drugs is one of the necessary preformulation steps in pharmaceutical product development research. The use of nanoparticles in the formulation of hydrophobic drugs improves their solubility and efficacy. Emulsion-solvent evaporation method, Double Emulsion and Evaporation method, Salting out method, Emulsions diffusion method, Antisolvent Precipitation Method, Polymerization method, and Coacervation or Ionic Gelation method can all be used to make nanoparticles. Bottom-up methods such as Antisolvent precipitation are the most efficient and cost effective in the preparation of nanoparticles. [ABSTRACT FROM AUTHOR]

The major aim of the current study is to develop a data-driven methodology based on green processing for estimation of drug solubility in supercritical carbon dioxide as the solvent. Several machine learning algorithms were utilized to simulate Capecitabine solubility in supercritical carbon dioxide for green pharmaceutical manufacturing applications which can enhance the solubility of drugs by this method of processing. In the models, the inputs are pressure (P) and temperature (T), and the target output (Y) is solubility. Tree-based ensemble models of RF (Random Forest), ET (Extra Tree), and GB (Gradient Boosting) were selected for modeling in this research in combination with the optimizer to model the process. The hyper-parameters of models were optimized to reduce the error in the fitting. The coefficient of determination (R2 score) values obtained more than 0.96 and RMSE (root mean square error) for ET, GB, and RF models are 2.91, 2.37, and 4.45, respectively. Based on accurate analyses of results Gradient Boosting selected for primary model in this research. The models were able to estimate the drug solubility which can be used to estimate solubility for a wide range, thereby saving time and costs of measurements. [ABSTRACT FROM AUTHOR]

Kojic acid (KA) is a BCS class II drug having low solubility and high permeability. This study was designed to enhance the aqueous solubility of KA, as well as its dissolution rate and, in turn, bioavailability, by formulating its smart nanocrystals. Nanocrystals of pure KA were formulated by the top-down method under high-pressure homogenization followed by freeze drying. The nanocrystals were evaluated for stability and other physical characteristics, including zeta sizer analysis, DSC, surface morphology, XRD, drug content, solubility, FTIR and in vitro drug release. The KA nanocrystals were found to be stable when kept at exaggerated conditions. The particle size of the nanocrystals was 137.5 ± 1.7, 150 ± 2.8, and 110 ± 3.0 nm for the F1, F2 and F3 formulations, respectively. There was negative zeta potential for all the formulations. The dispersity index was 0.45 ± 0.2, 0.36 ± 0.4 and 0.41 ± 1.5 for the F1, F2 and F3, respectively. The DSC studies showed that there was no interaction between the KA and the excipients of the nanocrystals. The morphological studies confirmed the presence of rough crystalline surfaces on the nanosized particles. XRD studies showed the successful preparation of nanocrystals. The drug content was in the official range of 90 ± 10%. The solubility of KA was significantly (p < 0.05) enhanced in the formulations of its nanocrystals as compared with pure KA powder. The ATR-FTIR studies revealed the presence of functional groups in both KA and KA-loaded nanocrystals, and no interaction was found between them. The nanocrystals released 83.93 ± 1.22% of KA in 24 h. The study concluded that the nanocrystals were successfully formulated using the top-down method followed by high-pressure homogenization. The solubility, as well as the dissolution, of the KA was enhanced, and this could improve the therapeutic effects of KA. [ABSTRACT FROM AUTHOR]

Telmisartan is an antihypertensive drug with low solubility and poor bioavailability. The goal of this study was to fabricate and characterize telmisartan nanoparticles to improve the dissolution and bioavailability of telmisartan. This study aims to tailor nanoparticles of telmisartan for the solubility and bioavailability enhancement by cost-effective technique. Telmisartan nanoparticles were prepared by antisolvent precipitation-ultrasonication technology using stabilizers and surfactants. The combination of hydroxypropyl methylcellulose-sodium dodecyl sulfate along with ultrasonication for 20 min was found to be effective for the stabilization of telmisartan nanoparticles. Stable nanoparticles of 52 nm particle size were obtained. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that the crystallinity of the drug was reduced in the nanoparticles. Saturation solubility and dissolution were increased due to the reduction in particle size and the amorphous nature of the drug in the formulated nanoparticles. An acute oral toxicity study of telmisartan nanoparticles was performed and concluded that nanoparticles of telmisartan at selected doses are not toxic and do not show mortality at the administered dose. Significant values of pharmacokinetic parameters—maximum plasma concentration and area under curve—have indicated better absorption of drug in the form of nanoparticles. The value of half-life of telmisartan nanoparticles (12.73 ± 0.59 h) was decreased compared to drug (26.86 ± 2.0 h), which concluded the increased oral absorption of telmisartan nanoparticles. All these findings reinforce the fact that the formulation of telmisartan nanoparticles is a new approach for solubility and bioavailability enhancement of telmisartan. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop resveratrol nanocrystals to solve low water solubility issues of resveratrol and adsorb them to the polycaprolactone nanofibers. Nanocrystals were prepared by microfluidization. Particle size, polydispersity index and zeta potential values were evaluated as dependent variables. Polycaprolactone (PCL) nanofibers were prepared via electrospinning method and the flow rate, electrical voltage and tip-to-collector distance were set to 3 mL/h, 13 kV and 15 cm, respectively. Optimum resveratrol nanocrystals were lyophilized and re-suspended in water and physically adsorbed to PCL nanofibers with two different concentrations (0.2 and 1 mg/cm2). Bioadhesion, wettability, solubility, drug loading and antimicrobial activity against Propionibacterium acnes studies were carried out. Final nanocrystals showed 800 nm of particle size, 0.4 of polydispersity index, and −8 mV of zeta potential. Nanocrystals successfully adsorbed to PCL nanofibers proven on SEM images with adsorption efficiencies >70%. Adsorption of resveratrol nanocrystals decreased the contact angle of PCL from 128° to 50°. The solubility of resveratrol nanocrystals enhanced ∼5-fold in comparison with coarse powder. Effective antimicrobial activity against P. acnes was observed. It is concluded that nanocrystal loading on nanofibers brings advantage into preparing easy to use dermal patches for acne treatment or skin disorders. [ABSTRACT FROM AUTHOR]

• Processing parameters were optimized based on the solubility of GA in SC−CO 2. • GA NPs were fabricated using SC−CO 2 -assisted RESOLV process. • The dissolution rate of GA was significantly enhanced after nanonization. • Nanosized GA has shown an excellent antiproliferative effect over raw GA. Despite the captivating interest for its potential anticancer efficacy against multiple types of cancer and ability to overcome multidrug resistance, the practical application of gambogic acid (GA) has been hampered by its poor water solubility. Herein, the fabrication of nanosized GA particles (251.2 nm ± 85.6 nm) using eco-friendly supercritical fluid (SCF)-assisted rapid expansion of a supercritical solution into a liquid solvent (RESOLV) process was demonstrated. The equilibrium solubility of GA in supercritical carbon dioxide (SC−CO 2) was initially determined at altered supercritical conditions (P: 10.0 MPa to 30.0 MPa, T: 308.15 K–328.15 K) and the obtained data points were then correlated using various density-based models including Méndez-Santiago and Teja, Bartle as well as Chrastil models. The solubility of GA in SC−CO 2 was found to be between 1.63 × 10−6 and 22.62 × 10−6 in terms of GA mole fraction, and considerably good correlation agreement was obtained with all the applied models and being the lowest deviations obtained with the Méndez-Santiago and Teja model. Furthermore, the fabricated GA nanoparticles (NPs) through benign RESOLV technique, were systematically characterized. Subsequently, in vitro antiproliferation tests resulted in its augmented antitumor efficacy due to enhanced solubility of GA. Together, the results have suggested that the benign RESOLV process has successfully fabricated nanosuspensions of GA with enhanced bioavailability and antineoplastic efficacy and may have great potential in pharmaceutics. [ABSTRACT FROM AUTHOR]

Nanoplex means drug nanoparticle forms a complex with oppositely charged polyelectrolyte. In this technique both cationic and anionic drugs forms a complex with its oppositely charged polyelectrolyte. In present work norfloxacin a class IV drug and polyanionic dextran sulfate was used as polyelectrolyte. In preparation of nanoplex norfloxacin was ionized with acidic solution gives cationic charges on drug it forms a complex with anionic dextran sulfate. In this process due to charge neutralization on drug it precipitates out in nanosize and strong electrostatic interaction between drug and polyelectrolyte prevents drug molecule to revert in its crystalline form. Hence process has capability of giving amorphous and nanosize formulation. Pluronic F 68 used as stabilizer and sodium chloride for its charge shielding effect. Nanoplex shows a particle size 346 nm, complexation efficiency 90%, drug loading 60% and stability for one month with 20 fold enhancement in solubility and dissolution rate. [ABSTRACT FROM AUTHOR]