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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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jo Klaveness, Werner Filtvedt and Hennie Marie Johnsen are inventors of a patent application with the title “Silicon particles for drug delivery”. The assignee of the patent application is Nacamed AS. Werner Filtvedt and Jo Klaveness have shares in Nacamed AS. Marianne Hiorth is an editor for the “Journal of Drug Delivery Science and Technology”., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

Drugs with poor water and lipid solubility are termed "brick dust." We previously successfully developed a co-amorphous system of a novel neuropeptide Y 5 receptor antagonist (AntiY 5 R), a brick dust molecule, using sodium taurocholate (NaTC) as a co-former. However, the maximum improvement in AntiY 5 R dissolution by the co-amorphous system was only approximately 10 times greater than that of the crystals. Therefore, in the current study, other bile salts, including sodium cholate (NaC), sodium chenodeoxycholate (NaCC), and sodium glycocholate (NaGC), were examined as co-formers to further improve AntiY 5 R dissolution. NaC, NaCC, and NaGC have glass transition temperatures above 150°C. All three co-amorphous systems prepared successfully retained the amorphous form of AntiY 5 R for 3 months at 40°C, but the co-amorphous system with NaGC (AntiY 5 R-NaGC; 1:9 molar ratio) provided the highest improvement in AntiY 5 R dissolution, which was approximately 50 times greater than that of the crystals. Possible intermolecular interactions via the glycine moiety of NaGC more than the other bile salts would contribute to the highest dissolution enhancement with AntiY 5 R-NaGC. Thus, NaGC would be a promising co-former for formulating stable co-amorphous systems to enhance the dissolution behavior of brick dust molecules., 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 B.V. All rights reserved.)

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.

Clays have been used in various health care products, including drug delivery systems. Advanced formulations have been investigated to take full advantage of clays or clay-based materials. The remarkable properties of clays, such as high adsorption, high surface area and high ion exchange capacities, provide an ideal system for the delivery of poorly water-soluble drugs. Currently, there is still limited information on the classification and discussion of clay-based formulations for poorly water-soluble drugs. This review aims to describe efficient delivery systems that use clay as the main excipient in formulations. More details regarding the strategies of using clays in formulations as well as fabrication methods will be discussed. Moreover, combinations with other excipients in hybrid formulations will also be mentioned and the efficacy of these systems will be evaluated. The recent studies on claybased formulations for poorly water-soluble drugs provide fundamental approaches and prospects to be applied in drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Porous carriers have been put forward as a promising alternative for stabilizing the amorphous state of loaded drugs, and thus significantly improving the dissolution rate of poorly soluble compounds. The purpose of this study was to enhance the saturation solubility, dissolution rate and drug loading of the poorly water-soluble drug silymarin via incorporation into mesoporous silica nanospheres within a lyophilized tablet to obtain a unique formulation. 3 2 full factorial design was applied to study the effect of both independent variables, polyvinyl alcohol (PVA) as stabilizer and binder and sucrose as cryoprotectant and disintegrant; and on the dependent variables that included the mean particle size (Y 1 ), disintegration time (Y 2 ), tablet strength (Y 3 ) and % of drug release after 2 min, R 2min ,Y 4 . The drug-loaded mesoporous silica nanospheres and the optimized formula was evaluated by different characterization methods: scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffractometry and Fourier transform infrared spectroscopy; as well as drug content, saturation solubility and moisture content. The evaluation demonstrated that the loaded mesoporous silica nanospheres and the optimized formula are in amorphous state without any chemical interaction with the silica matrix or the stabilizer. Moreover, the drug was stably maintained in nanosize range with narrow particle size distribution. Furthermore, the optimized lyophilized tablets had highly porous structure, low friability (less than 1%), fast disintegration (less than 30 s), high tablet strength, low moisture content (less than 1%), remarkably increased dissolution rate and noticeable improvement in saturation solubility., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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]

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]

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]

[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]

Objectives: The current objective of the present study was to enhance the solubility and dissolution rate of the antiviral drug atazanavir sulphate by employing nanocrystallization technique. Materials and Methods: The method employed for increment of solubility was nanocrystallization which is based on the reduction of particle size of the drug thereby increasing its solubility and also its dissolution property. Various polymers in different ratios were used like HPMC K15M, PVP K30 and PEG 6000. Results: Drug and polymers were firstly tested for their interaction between each other's and it was found that the drug and polymers are compatible with each other. From the solubility study it was seen that the solubility of the optimized batch was increased to 40.068mg/ml in distilled water and 160.182mg/ml in phosphate buffer while the pure drug shows the solubility of 4.174mg/ml in distilled water and 20.547mg/ml in phosphate buffer. The percent drug release of the optimized formulation was seen of 87.91% in 2 hrs which was maximum from all the other batches. The stability study revealed that the prepared nanocrystal does not show any insignificant changes and therefore it can be concluded as stable. Conclusion: The prepared nanocrystals are the proof that this method of nanocrystallization may prove to be an efficient method in increasing the solubility and dissolution rate of the drug which are having low solubility and low bioavailability. [ABSTRACT FROM AUTHOR]

Aim: Self nano-emulsifying drug delivery system (SNEDDS) of candesartan cilexetil was explored to enhance its oral bioavailability. SNEDDS has tremendous potential in enhancing oral bioavailability of poorly aqueous soluble therapeutic agents. SNEDDS are pre-concentrate mixture of oil, surfactant and co-surfactant produces nanoemulsion after oral administration due to mild agitation produced by gastro motility within the size range of 20-200nm. Methodology: The formulations were developed by selecting capmul MCM®, triacetin® and caprylic acid® under the oil phase based on solubility of drug; cremophore RH40®, brij35® under surfactants category and transcutol P under co-surfactant on basis of their emulsification property. Optimum concentrations were choosen from the Terinary phase diagrams and evaluated for their properties. Results: From the results of ternary diagrams 16 formulations were selected (A1, A2, A3, A4, B1, B2, C1, C2, C3, C4, D1, D2, E1, E2, F1, F2) and subjected to characterization studies. Best formulations were subjected to particle size analysis and in vitro release studies. Among selected formulations, A1 and C1 have shown high in vitro drug release profiles with less selfemulsification time having grade A dispersibility without any precipitation and phase separation. Discussion: Concentration of surfactant helps in reducing the size of the particle when compared to the co-surfactant concentration. Enhanced dissolution of candesartan cilexitil may be attributed to the spontaneous formation of nanoemulsion in vitro with a decreased particle size that leads to the increased surface area leaving the drug candesartan as finely dispersed particles in dissolution media. Conclusion: Formulation C1 consists of triacetin oil 30% w/w, cremophore RH 40 6%w/w and transcutol P 64%w/w showed best emulsification characteristics like 99% percent transmittance, with increased dissolution profile (98%) than pure drug (45%) with nano range goblet size (165.9nm). [ABSTRACT FROM AUTHOR]

With the advent of high throughput screening, drugs are emerging to be more lipophilic and less hydrophilic. Liquisolid Technology aims at solubility enhancement of such entities via cosolvency concept in a relatively minimalistic setup where there is no need of sophisticated machinery and is cost effective. It involves constituting a drug into molecular dispersion via a non-volatile solvent and then transforming it into a dry looking, free flowing compressible powder. This article aims at mapping Liquisolid Technology where its preparation techniques and potential applications are reviewed. An overview of the performance of Liquisolid in areas of dissolution enhancement, zero order release, photostability enhancement, liquipellets and its role in natural product formulations is recorded for a number of drugs. [ABSTRACT FROM AUTHOR]

The present study demonstrated the binary and ternary complexes of Zaltoprofen (ZPF) with β-CD and HP-β-CD. The products were characterized using solubility, in vitro dissolution, and DSC studies. The mode of interaction of guest and host was revealed through 1 H NMR and FT-IR studies. A significant increase was noticed in the stability constant (K c ) and complexation efficiency (CE) of β-CD and HP-β-CD due to addition of L-Arg in ternary complexes. The ternary complexes showed greater increase in solubility and dissolution of ZPF than binary complexes. Thus, ternary system of ZPF could be an innovative approach for its solubility and dissolution enhancement. [ABSTRACT FROM AUTHOR]

The cogrinding technique is one of most effective methods for improving the dissolution of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental standpoint, as the technique does not require any toxic organic solvents. Present work explores the role ofd-glucosamine HCl (GL) as a potential excipient to improve dissolution of a low melting point drug, ibuprofen (Ibu), using physical mixtures and coground formulations. The dissolution of the poorly soluble drug has been improved by changing the ratio of Ibu:GL and also grinding time. The results also showed that although GL can enhance the solubility of Ibu, it also reduces pH around the Ibu particles which led to poor dissolution performance when the concentration of GL is high. The effect of GL on the solubility of Ibu could be misleading if the pH of the final solution was not measured. Grinding reduced the particle size of GL significantly but in case of Ibu it was less effective. Solid state analysis (XRPD, DSC, and FT-IR) showed that ibuprofen is stable under grinding conditions, but the presence of high concentration of GL in samples subjected to high grinding times caused changes in FT-IR spectrum of Ibu which could be due to intermolecular hydrogen bond or esterification between the carboxylic acid group in the ibuprofen and hydroxyl group in the GL. [ABSTRACT FROM AUTHOR]

Abstract: Dissolution enhancement of poorly water-soluble Irbesartan drug through formation of Irbesartan-silica based microcapsules has been investigated. The microcapsules were fully characterized using FTIR, DSC, XRD and SEM techniques. Pre-adjusted pH method has been utilized to form efficient Irbesartan–silica based microcapsules capable to enhance dissolution rate of Irbesartan drug at the challenging pH 5.5 value. The formed Irbesartan–silica based microcapsules showed large dissolution increase as Neusilin feed ratio and as pre-adjusted pH were increased. The maximum dissolution enhancement was achieved via salt formation at pre-adjusted pH 7.4 and 1:3 ratio of Irbesartan-silica based microcapsules. The successful dissolution enhancement was owed to destruction of the crystallinity of the drug accompanied with Irbesartan-silica based salt formation at elevated pH pre-adjustment leading to apparent drug dissolution. [Copyright &y& Elsevier]

Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System – BCS) administered in single drug products or as fixed dose combinations. The aim of the present series of experiments was to improve the solubility and dissolution of two fixed dose combination formulations (FDC), each consisting of two BCS class II drugs. The first FDC contained a weak acid (glimepiride) and a weak base (pioglitazone), while the second FDC contained two compounds (simvastatin and ezetimibe) that are essentially non-ionised over the physiological pH range. The formulation approaches used were as follows: (a) an inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD), (b) a solid dispersion with Soluplus®, a new highly water soluble polyvinyl caprolactam – polyvinyl acetate – polyethylene glycol graft copolymer and (c) a ternary inclusion complex with both HP-β-CD and Soluplus®. Solid state analysis was performed for the pure drugs, and all formulations using powder X-ray diffraction (PXRD). The in vitro performance of the different formulation approaches, as gauged by solubility and dissolution experiments, was compared with that of the marketed products containing the respective fixed dose combinations, Tandemact® 30mg/4mg tablets and Inegy® 10mg/40mg tablets. The FDCs of the pure drugs and the marketed products showed very poor (and especially for pioglitazone, strongly pH-dependent) dissolution. By contrast, all binary and ternary inclusion complexes showed enhanced release for both drugs in the FDC. The ternary inclusion complex generated synergistic improvement in solubility and dissolution results for both FDCs. For example, in pH conditions of the fasted small intestine after a test duration of 240min, we observed 100% dissolution of both drugs from the ternary pioglitazone/glimepiride (30mg/4mg) complex formulation, whereas from the marketed formulation less than 5% pioglitazone, and only 25% glimepiride dissolved. Using the same conditions, 60% ezetimibe and 85% simvastatin dissolved from the ternary ezetimibe/simvastatin (10mg/40mg) complex formulation, whereas with less than 5% ezetimibe and 10% simvastatin dissolved after 240min, the marketed FDC formulation showed poor dissolution. Based on the results of the present study, the bioavailability of both drugs in the fixed dose combination is likely to be increased after oral administration of the new formulations, especially when the fixed dose combination is formulated as a ternary complex consisting of HP-β-CD and Soluplus®. [ABSTRACT FROM AUTHOR]

Enhancement of the dissolution rate of poorly soluble compounds through the formation of drug-drug eutectics was investigated using fenofibrate and acetylsalicylic acid. Solid-liquid equilibria in the system under study were investigated by differential scanning calorimetry (DSC). The phase diagram for the whole range of compositions was constructed. In addition, existence of a metastable polymorph of fenofibrate has been confirmed. The investigation has revealed that acetylsalicylic acid and fenofibrate form a simple eutectic mixture containing 0.958 mol fraction of fenofibrate at the eutectic point. Dissolution rate improvement of fenofibrate correlated with the phase diagram. The amount of fenofibrate released from the solid dispersions that contained fenofibrate as the eutectic mixture with acetylsalicylic acid was at least threefold higher compared to untreated fenofibrate. [ABSTRACT FROM AUTHOR]

Background: Dissolution testing is an important test for judging the effectiveness of a pharmaceutical dosage form. Many drugs create adverse effect because of insufficient solubility at the physiological pH. This study is aimed to improve the dissolution properties of prednisolone (PRD) that falls under the category of class II biopharmaceutics system. Methods: In this study, preparation of solid dispersions with various water-soluble carriers was studied to improve the dissolution of PRD. To obtain the optimized formulation, solid dispersions were prepared employing different methods using different carriers with various drug:carrier ratios. Their dissolution behaviors were also compared. Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction, and thermal analysis were studied to characterize the prepared solid dispersion. Results: PRD formed stable complexes with carriers as indicated by the stability constants ( Ka) of 9.5--597.2 M−−1. The results indicated that in vitro dissolution rate of PRD was remarkably improved in the solid dispersion of the drug compared with physical mixture and drug alone. This can be attributed to improved wettability, dispersibility, decrease in crystallinity, and increase in amorphous fraction of the drug. The results obtained from Fourier transform infrared spectroscopy and powrer X-ray diffraction showed good evidence of drug--carrier interaction while using carriers such as hydroxypropyl-ββ-cyclodextrin (HP-ββCD) and polyethylene glycol (PEG). Crystallinity of the drug was reduced in the solid dispersions prepared with hydroxypropyl-ββ-cyclodextrin, polyvinylpyrrolidone-co-vinyl acetate 64, and PEG as revealed from the differential scanning calorimetry thermograms. Conclusion: The results suggested that the solid dispersion with selected excipients is a powerful tool to accelerate the dissolution of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

The aim of the present study was to improve the solubility, and therefore the dissolution of poorly water-soluble allopurinol. Solid dispersions of allopurinol were prepared with different polymers or carriers such as polyvinylpyrrolidone (PVP K30 and PVP K90), polyethylene glycol (PEG 4000 and PEG 6000), urea and mannitol at two drug : carrier ratios (1:1) and (1:2). Different methods such as melting and solvent evaporation methods were used to improve dissolution characteristics and solubility of allopurinol. The solid dispersions were characterized using a differential scanning calorimeter (DSC) and X-ray diffraction (XRD) while the interactions which took place were identified with fourier transform infrared (FTIR) spectroscopy. Due to formation of hydrogen bonds between allopurinol and urea and mannitol, a transition of allopurinol from the crystalline to amorphous state was achieved. The DSC thermograms of the solid dispersions indicated the potential of heat induced interactions between allopurinol and the carriers used could influence dissolution rate of the drug. The dissolution amount (%) of pure allopurinol was 80% at 45 min. F5, F3, F6, F7, and F1 showed better dissolution percentages of 100, 93, 92.4, 90.6, and 89%, respectively, at 45 min. [ABSTRACT FROM AUTHOR]

Abstract: In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4mg) in a small liquid volume (3ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1 N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations. [Copyright &y& Elsevier]

The objective of the present study was to coprocess 2 active pharmaceutical ingredients (APIs), nevirapine (NVP) and stavudine (STV), by spray drying technique to overcome the respective problems of poor solubility and poor content uniformity. The coprocessed product (NVP-STV CP) and untreated APIs were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size, surface area analysis, compressibility, and solubility. Coprocessing enhanced NVP solubility by ∼1.5 fold and provided uniform distribution of low-dose STV in the formulation composite. Phase solubility studies elucidated the mechanism of enhanced NVP solubility. The coprocessed product was stable under accelerated stability conditions of 40°C/75% relative humidity (RH) for 3 months. The coprocessed product was formulated into 3 drug fixed dose combination (FDC) tablets with lamivudine (LMV), which gave an enhanced in vitro NVP drug release compared with the control formulation. Spray drying as a coprocessing technique optimally utilized the individual components of the antiretroviral FDC tablets and synergistically enhanced the performance attributes. [ABSTRACT FROM AUTHOR]

• Irbesartan microparticles and its composite microparticles were prepared by the ASES process for the first time. • The physicochemical of Irbesatan and the its composites were investigated and compared. • The solubility and dissolution rate of Irbesatan microparticles were improved obviously. • ASES Irbesartan composite microparticles should be a candidate for drug delivery system. In this study, irbesartan (IST) microparticles, an IST /hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex, and an IST/polyvinylpyrrolidone (PVP) complex were prepared using a supercritical aerosol solvent extraction system (ASES). The goal was to improve the solubility and dissolution rate of IST, which is an angiotensin II receptor blocker and exhibits solubility-limited oral bioavailability in pharmacokinetics. It is noteworthy that these three drug delivery systems show a higher solubility and dissolution rate of IST compared with raw IST. Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy analyses were conducted to study the physicochemical properties of IST before and after ASES processing, and to confirm the formation of the IST complexes with HP-β-CD and PVP. This study provides valuable information for the potential clinical application of IST microparticles and IST composite particles synthesized using the ASES process. [ABSTRACT FROM AUTHOR]