Solvent-free method for masking the bitter taste of azithromycin dihydrate using supercritical fluid technology.

INTRODUCTION AND PURPOSE: The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 - 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. METHODS: A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. RESULTS: The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste. CONCLUSIONS: Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.

The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel.

Hydroxychloroquine (HCQ) was repurposed for COVID-19 treatment. Subtherapeutic HCQ lung levels and cardiac toxicity of oral HCQ were overcome by intratracheal (IT) administration of lower HCQ doses. The crosslinker-free supercritical fluid technology (SFT) produces aerogels and impregnates them with drugs in their amorphous form with efficient controlled release. Mechanistic physiologically based pharmacokinetic (PBPK) modeling can predict the lung's epithelial lining fluid (ELF) drug levels. This study aimed to develop a novel HCQ SFT formulation for IT administration to achieve maximal ELF levels and minimal cardiac toxicity. HCQ SFT formulation was prepared and evaluated for physicochemical, in vitro release, pharmacokinetics, and cardiac toxicity. Finally, the rat HCQ ELF concentrations were predicted using PBPK modeling. HCQ was amorphous after loading into the chitosan-alginate nanoporous microparticles (22.7±7.6 µm). The formulation showed a zero-order release, with only 40% released over 30 min compared to 94% for raw HCQ. The formulation had a tapped density of 0.28 g/cm3 and a loading efficiency of 35.3±1.3%. The IT administration of SFT HCQ at 1 mg/kg resulted in 23.7-fold higher bioavailability, fourfold longer MRT, and eightfold faster absorption but lower CK-MB and LDH levels than oral raw HCQ at 4 mg/kg. The PBPK model predicted 6 h of therapeutic ELF levels for IT SFT HCQ and a 100-fold higher ELF-to-heart concentration ratio than oral HCQ. Our findings support the feasibility of lung-targeted and more effective SFT HCQ IT administration for COVID-19 compared to oral HCQ with less cardiac toxicity. Graphical abstract.

In vivo tests of a novel wound dressing based on agar aerogel.

Aerogels, especially bio-based ones, present a promising option for wound dressing; specifically, because of their low toxicity, high stability, bio-compatibility, and good biological performance. In this study, agar aerogel was prepared and evaluated as novel wound dressing material in an in vivo rat study. Agar hydrogel was prepared by thermal gelation, after that the water inside the gel was exchanged with ethanol, and finally the alcogel was dried by supercritical CO2. The textural and rheological properties of the prepared aerogel were characterized, showing that the prepared agar aerogels possess high porosity (97-98 %), high surface area (250-330 m2g-1) as well as good mechanical properties and easiness of removal from the wound site. The results of the in vivo experiments macroscopically demonstrate the tissue compatibility of the aerogels in dorsal interscapular injured rat tissue and a shorter wound healing time comparable to that of gauze-treated animals. The histological analysis underpins the reorganisation and healing of the tissue for the injured skin of rats treated with agar aerogel wound dressing within the studied time frame.

Insights into the mapping of green synthesis conditions for ZnO nanoparticles and their toxicokinetics.

Research on ZnO nanoparticles (NPs) has broad medical applications. However, the green synthesis of ZnO NPs involves a wide range of properties requiring optimization. ZnO NPs show toxicity at lower doses. This toxicity is a function of NP properties and pharmacokinetics. Moreover, NP toxicity and pharmacokinetics are affected by the species type and age of the animals tested. Physiologically based pharmacokinetic (PBPK) modeling offers a mechanistic platform to scrutinize the colligative effect of the interplay between these factors, which reduces the need for in vivo studies. This review provides a guide to choosing green synthesis conditions that result in minimal toxicity using a mechanistic tool, namely PBPK modeling.

Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Evaluation of EDTA Dianhydride Versus Diphenyl Carbonate Nanosponges for Curcumin.

Cyclodextrin-based nanosponges are widely investigated for several applications and are considered potential drug carriers. The method of nanosponges preparation involves the use of chemical cross-linking agents where the properties of Nanosponges can be affected. This study compared the resulting differences in the final nanosponges' properties using carbonate and dianhydride crosslinkers. Diphenyl carbonate and EDTA dianhydride were used for the synthesis of nanosponges. Both types of nanosponges were loaded with curcumin as a model drug. Physicochemical characterizations, including PXRD, DSC, FTIR, scanning electron microscopy, AFM, particle size, zeta potential, and surface area analysis, were carried out for the prepared nanosponges. Curcumin release and drug content were also evaluated. Nanosponges prepared by Diphenyl carbonate crosslinker resulted in an amorphous form compared to crystalline EDTA-nanosponges. This study reported the successful inclusion and complexation of curcumin inside carbonate cross-linked cyclodextrin-based nanosponges and suggested the physical entrapment of crystalline curcumin in EDTA dianhydride. These findings were further investigated and supported by computational modeling.

Weak complexation of 5-fluorouracil with ß-cyclodextrin, carbonate, and dianhydride crosslinked ß-cyclodextrin: in vitro and in silico studies.

Background and purpose: Several pharmaceutical formulations were investigated to improve the solubility of 5-fluorouracil to enhance bioavailability and therapeutic efficacy. This study aimed to examine the potential use of cyclodextrin-based nanosponges for the incorporation of 5-fluorouracil and to investigate the use of different crosslinking agents on the properties of the resulting drug carrier. 5-Fluorouracil complexation with ß-cyclodextrin was also studied to explain the unexpected results of weak 5-fluorouracil incorporation in nanosponge. Experimental approach: Nanosponges were synthesized by crosslinking ß-cyclodextrin with two different crosslinkers; diphenyl carbonate and ethylenediaminetetraacetic dianhydride. The incorporation of 5-fluorouracil into ß-cyclodextrin and the prepared nanosponges were assessed by NMR, FTIR, PXRD, DSC, and TGA. In addition, an in vitro release study was carried out to evaluate the potential use of ß-cyclodextrin- based nanosponges as pharmaceutical formulations for 5-fluorouracil. Findings / Results: Physicochemical characterization of the dried formulations indicated the complexation of 5-fluorouracil with the ß-cyclodextrin polymer. Despite that, no clear manifestation of 5-fluorouracil encapsulation in the prepared ß-cyclodextrin-based nanosponge was detected. Furthermore, no significant differences were observed in the release profiles of 5-fluorouracil, ß-cyclodextrin complex, and ß- cyclodextrin-based nanosponge, suggesting weak complexation and instability in aqueous solutions. EDTA- crosslinked ß-cyclodextrin-based nanosponge showed a slight improvement in 5-fluorouracil solubility with a faster initial rate of 5-fluorouracil release. Conclusion and implications: This study suggested weak complexation between 5-fluorouracil and the ß- cyclodextrin polymer or nanosponges. Crosslinking of ß-cyclodextrin with EDTA dianhydride crosslinker showed an enhancement in 5-fluorouracil saturation solubility combined with a faster initial rate of drug release.

Enhancing Atorvastatin In Vivo Oral Bioavailability in the Presence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Using Supercritical Fluid Technology Guided by wbPBPK Modeling in Rat and Human.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are common disorders that can change the body's physiology and drugs pharmacokinetics. Solid dispersion (SD) preparation using supercritical fluid technology (SFT) has many advantages. Our study aimed to explore the effect of IBS and IBD on atorvastatin (ATV) pharmacokinetics, enhance ATV oral bioavailability (BCS II drug) using SFT, and analyze drug-disease-formulation interaction using a whole-body physiologically based pharmacokinetic (wbPBPK) model in rat and human. A novel ATV formulation was prepared using SFT and characterized in vitro and in vivo in healthy, IBS, and IBD rats. The resulting ATV plasma levels were analyzed using a combination of conventional and wbPBPK approaches. The novel formulation increased ATV solubility by 20-fold and resulted in a zero-order release of up to 95%. Both IBS and IBD increased ATV exposure after oral and intravenous administration by more than 30%. The novel SFT formulation increased ATV bioavailability by 28, 14, and 18% in control, IBD, and IBD rat groups and resulted in more consistent exposure as compared to raw ATV solution. Higher improvements in ATV bioavailability of more than 2-fold upon receiving the novel SFT formulation were predicted by the human wbPBPK model as compared to receiving the conventional tablets. Finally, the established wbPBPK model could describe ATV ADME in the presence of IBS and IBD after oral administration of raw ATV and using the novel SFT formula and can help scale the optimized ATV dosing regimens in the presence of IBS and IBD from rats to humans.

Co-crystallization of Amoxicillin Trihydrate and Potassium Clavulanate Provides a Promising Approach for Preparation of Sustained-Release Microspheres.

This work aimed to prepare sustained-release microspheres for amoxicillin trihydrate and potassium clavulanate. Co-crystals of amoxicillin trihydrate and potassium clavulanate were prepared using three different techniques, including supercritical fluid technology. Full characterization was performed for the prepared co-crystals, including molecular dynamic simulation. Next, the co-crystals were microencapsulated with ethylcellulose using the emulsion solvent evaporation method in spherical microspheres. Physicochemical characterizations for the prepared co-crystal were performed using FTIR, DSC, and PXRD. Finally, scanning electron microscopy was used to assess the morphology of the prepared microspheres. Physicochemical studies showed the solid-state interaction between amoxicillin trihydrate and potassium clavulanate in the prepared co-crystals. The total energy suggested differences between the three methods of co-crystal preparations suggesting some structural changes have occurred with better stabilization at supercritical fluid technology. Encapsulation of the co-crystals was successfully performed using ethylcellulose polymer. The in vitro release studies revealed sustained-release profiles for the co-crystal microspheres. Potassium clavulanate was released at a lower rate from the crystal microspheres prepared using co-crystals than the release in microspheres of potassium clavulanate alone. The empirical Higuchi model best fitted the in vitro release profile for amoxicillin trihydrate-potassium clavulanate co-crystal microspheres.

Preparation and Evaluation of Polyvinylpyrrolidone Electrospun Nanofiber Patches of Pioglitazone for the Treatment of Atopic Dermatitis.

Nanofibers have many promising biomedical applications. They can be used for designing transdermal and dermal drug delivery systems. This project aimed to prepare and characterize polyvinylpyrrolidone-based nanofibers as a dermal and transdermal drug delivery system using pioglitazone. Pioglitazone is an oral antidiabetic drug. In addition, it can act as an inflammatory process modulator, making it a good candidate for managing different skin inflammatory conditions such as atopic dermatitis, skin ulcers, and diabetic foot wound healing. Several nanofiber formulations were prepared using the electrospinning method at different drug loadings, polyvinylpyrrolidone concentrations, and flow rates. A cast film with the exact composition of selected nanofiber formulations was prepared as a control. Nanofibers were characterized using a scanning electron microscope to calculate the diameter. Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction were performed for physical and biochemical characterizations. In vitro release, drug loading efficiency, and swelling studies were performed. Ex vivo permeation studies were performed using Franz diffusion cells with or without applying a solid microneedle roller. Round uniform nanofibers with a smooth surface were obtained. The diameter of nanofibers was affected by the drug loading and polymer concentration. Fourier-transform infrared spectra showed a potential physical interaction between the drug and the polymer. According to X-ray diffraction, pioglitazone existed in an amorphous form in prepared nanofibers, with partial crystallinity in the casted film. Nanofibers showed a higher swelling rate compared to the casted film. The drug dissolution rate for nanofibers was 2.3-folds higher than the casted films. The polymer concentration affected the drug dissolution rate for nanofibers; however, drug loading and flow rate did not affect the drug dissolution rate for nanofibers. The application of solid microneedles slightly enhances the total amount of drug permeation. However, it did not affect the flux of the drug through the separated epidermis layer for pioglitazone. The drug permeation flux in nanofibers was approximately five times higher than the flux of the casted film. It was observed that pioglitazone is highly retained in skin layers. Graphical abstract.

Evaluation and Characterization of Curcumin-ß-Cyclodextrin and Cyclodextrin-Based Nanosponge Inclusion Complexation.

Cyclodextrin polymers and cyclodextrin-based nanosponges have been widely investigated for increasing drug bioavailability. This study examined curcumin's complexation stability and solubilization with ß-cyclodextrin and ß-cyclodextrin-based nanosponge. Nanosponges were prepared through the cross-linking of ß-cyclodextrin with different molar ratios of diphenyl carbonate. Phase solubility experiments were conducted to evaluate the formed complexes and evaluate the potential of using ß-cyclodextrin and nanosponge in pharmaceutical formulations. Furthermore, physicochemical characterizations of the prepared complexes included PXRD, FTIR, NMR, and DSC. In addition, in vitro release studies were performed for the prepared formulations. The formation of ß-cyclodextrin complexes enhanced curcumin solubility up to 2.34-fold compared to the inherent solubility, compared to a 2.95-fold increment in curcumin solubility when loaded in ß-cyclodextrin-based nanosponges. Interestingly, the stability constant for curcumin nanosponges was (4972.90 M-1), which was ten times higher than that for the ß-cyclodextrin complex, where the value was 487.34 M-1. The study results indicated a decrease in the complexation efficiency and solubilization effect with the increased cross-linker amount. This study's findings showed the potential of using cyclodextrin-based nanosponge and the importance of studying the effect of cross-linking density for the preparation of ß-cyclodextrin-based nanosponges to be used for pharmaceutical formulations.

Fabrication and Evaluation of Transdermal Delivery of Carbamazepine Dissolving Microneedles.

This project aims to prepare hydrogel microneedle patches (MNs) as a painless method to deliver carbamazepine transdermally. This can be used as a sustained release system that offers the advantages of lower gastrointestinal side effects and avoids the first-pass metabolism of the drug. MNs were composed of two medicated layers, a microneedle layer and a base layer. MNs were fabricated using polyvinyl alcohol with or without polyvinylpyrrolidone Kollidon 30 as a matrix polymer and in the presence of selected solubilizing agent (polyethylene glycol 400, Tween 80, or α-tocopherol polyethylene glycol). Freezing-thawing cycle was evaluated as one of the processing parameters that may affect the drug release. The MNs were evaluated for their weight variation, base thickness, and content uniformity. The physicochemical compatibility between carbamazepine and the polymers was estimated by Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray powder diffraction. Evaluation for the in vitro release studies and ex vivo permeation studies was performed. The prepared MNs were flexible, clear, and uniform in weight, base thickness, and drug content. Physicochemical characterizations showed that carbamazepine was amorphous in most of the MNs. In vitro release and ex vivo permeation studies of carbamazepine were significantly higher for MNs containing a combination of 1:1 w/w of PEG 400 and Tween 80 as solubilizing agents where the release was extended over 96 h, with the release of 85.2% and 59.6% permeation percentage compared to other MNs. A significant effect of the freezing-thawing cycle on the release profile of the drug was observed. The hydrogel MNs are shown to be stable under the studied storage conditions.

Development and Evaluation of Cocoa Butter Taste Masked Ibuprofen Using Supercritical Carbon Dioxide.

Masking the unpleasant taste of the pharmaceutically active ingredients plays a critical role in patient acceptance, particularly for children. This work's primary objective was the preparation of taste-masked ibuprofen microparticles using cocoa butter with the assistance of supercritical fluid technology. Microparticles were prepared by dissolving ibuprofen in melted cocoa butter at 40 °C. The solution was then introduced into a supercritical fluid unit and processed at 10 MPa CO2 pressure for 30 min. The product was collected after depressurizing the system. The effect of the drug to cocoa butter ratio and the supercritical fluid units' configuration on product quality was evaluated and compared with the sample prepared by a conventional method. Physicochemical characterization of the prepared product, including particle size, crystallinity, entrapment efficiency, in vitro drug release, and product taste using a human volunteer panel was conducted. The produced microparticles were in the range of 1.42 to 15.28 µm. The entrapment efficiency of the formulated microparticles ranged from 66 to 81%. The drug:polymer ratio, the configuration of the supercritical fluid unit, and the method of preparation were found to have a critical role in the formulation of ibuprofen microparticles. Taste evaluation using human volunteers showed that microparticles containing 20% drug and processed with supercritical fluid technology were capable of masking the bitter taste of ibuprofen. In conclusion, the dispersion of ibuprofen in cocoa butter using supercritical fluid technology is a a promising innovative method to mask the bitter taste of ibuprofen.

Preparation of Hybrid Alginate-Chitosan Aerogel as Potential Carriers for Pulmonary Drug Delivery.

This study aims to prepare hybrid chitosan-alginate aerogel microparticles without using additional ionic crosslinker as a possible pulmonary drug delivery system. The microparticles were prepared using the emulsion gelation method. The effect of the mixing order of the biopolymer within the emulsion and the surfactant used on final particle properties were investigated. Physicochemical characterizations were performed to evaluate particle size, density, morphology, surface area, surface charge, and the crystallinity of the preparation. The developed preparation was evaluated for its acute toxicity in adult male Sprague-Dawley rats. Measurements of zeta potential suggest that the surface charge depends mainly on the surfactant type while the order of biopolymer mixing has less impact on the surface charge. Chitosan amphiphilic properties changed the hydrophilic-lipophilic balance (HLB) of the emulsifying agents. The specific surface area of the prepared microparticles was in the range of (29.36-86.20) m2/g with a mesoporous pore size of (12.48-13.38) nm and pore volume of (0.09-0.29) cm3/g. The calculated aerodynamic diameter of the prepared particles was in the range of (0.17-2.29 µm). Toxicity studies showed that alginate-chitosan carrier developed herein caused mild lung inflammation with some renal and hepatic toxicities.

Willingness and readiness to test for COVID-19; A qualitative exploration of community pharmacists.

OBJECTIVES: The present study aimed to exploring community pharmacists' willingness and readiness to test for COVID-19 in Jordan. METHODS: Purposeful sampling was used to identify a list of 30 community pharmacies, which were approached to participate in the study. Twenty interviews were needed to reach data saturation. In-depth interviews were conducted, recorded, transcribed, and analysed using NVivo 11 Software. Interviews followed a previously prepared and validated 10-item interview guide. The interview guide discussed pharmacists' willingness and readiness to test for COVID-19. RESULTS: Twenty community pharmacists were interviewed for the purpose of the present study. Interviews took place during April 2020 and the mean interview duration was 23.30 minutes. Respondents had a mean age of 36.4 years and a mean experience of 8.8 years. The majority were female (70%) and 50% held a BSc in Pharmacy. Regarding respondents' willingness to test for COVID-19 emerging themes were helping other healthcare professional, willingness to contribute to official efforts in fighting COVID-19, acting as an accessible testing cite, willingness to carry out home testing. Regarding respondents' readiness to test for COVID-19 emerging themes were Pharmacists lack basic testing skills, pharmacies are not ready to preform tests and the need for training and certifying. CONCLUSION: Jordanian pharmacists are willing to test patients for COVID-19 in community pharmacies, however, they thought they are not ready enough to undergo such tests and needed extra training and better safety precautions.

Development, In Vitro Characterization, and In Vivo Toxicity Evaluation of Chitosan-Alginate Nanoporous Carriers Loaded with Cisplatin for Lung Cancer Treatment.

Polysaccharide-based aerogels are promising drug carriers. Being nanoporous with a high specific surface area allows their use as a drug vehicle for various delivery routes. Intratracheal and intravenous administration of free cisplatin causes toxicity in the rat liver, lungs, and kidneys. In this work, microspherical particles based on alginate-chitosan without a traditional crosslinker were evaluated for targeted delivery of cisplatin by intratracheal administration. The aerogel particles were prepared using the emulsion gelation method, followed by supercritical carbon dioxide extraction. Loading of cisplatin on the prepared porous particles was performed by impregnation using supercritical fluid technology. The prepared carrier and the loaded drug were evaluated for drug content, release, and in vivo acute and subacute toxicity. Cisplatin was successfully loaded (percent drug loading > 76%) on the prepared carrier (particle size = 0.433 ± 0.091 µm) without chemically interacting with the carrier and without losing its crystal form. Sixty percent of cisplatin was released within 2 h, and the rest was loaded inside the polymer pores and had a sustained first-order release over 6 h. Loading cisplatin on the carrier developed herein reduced the cisplatin lung toxicity but increased the liver toxicity after intratracheal administration with nephrotoxicity being proportional to cisplatin dose in case of carrier-loaded cisplatin. Moreover, loading cisplatin on the carrier significantly reduced mortality rate and prevented weight loss in rats as compared to free cisplatin in subacute studies after intratracheal administration. Thus, the developed carrier showed high potential for targeted delivery of cisplatin for lung cancer treatment by inhalation. Graphical abstract.

Enhancement of dissolution of atorvastatin through preparation of polymeric solid dispersions using supercritical fluid technology.

BACKGROUND AND PURPOSE: This study aimed at preparation of solid dispersions in order to enhance dissolution of poorly water-soluble atorvastatin using supercritical CO2 technology. Atorvastatin has poor bioavailability of 12%, mainly due to poor water solubility and dissolution. Dispersion of drugs in various hydrophilic carriers using supercritical fluid technology has been found to be an outstanding method to prepare solid dispersion. EXPERIMENTAL APPROACH: Four different polymers were employed. These were polyvinyl pyrrolidone K30 (PVP), polyethylene glycol 6000 (PEG), Soluplus®, and chitosan. Full physicochemical characterizations were performed in addition to in vitro dissolution study. FINDINGS / RESULTS: The used polymers enhanced the dissolution rate of atorvastatin. However, supercritical parameters affected the dissolution profile and drug loading efficiency of the prepared dispersions. High performance liquid chromatography assay indicated the stability of the prepared PEG, Soluplus® and chitosan-based dispersions. On the other hand, PVP solid dispersions were not stable and formed sticky paste. Powder X-ray diffraction showed similar patterns for PEG-based dispersions after exposure to storage condition, while the intensity of atorvastatin peaks increased after three months of storage of Soluplus® and chitosan dispersions. CONCLUSION AND IMPLICATIONS: Supercritical fluid technology proved to have great potential to prepare dispersions for biopharmaceutics classification system (BCS) class II drugs. Dissolution enhancement of atorvastatin was achieved through successful preparation of polymeric dispersions of the drug using the supercritical technology without further addition of solvents.

A Comparative Solubility Enhancement Study of Cefixime Trihydrate Using Different Dispersion Techniques.

This study aimed to investigate the effect of different polymers (polyethylene glycol 4000 and 6000 and Soluplus®) on the enhancement of solubility, dissolution, and stability of cefixime trihydrate as a selected class II model drug. Different solid dispersions have been prepared using conventional methods and supercritical fluid technology. The effect of co-solvent incorporation in supercritical fluid technology was also studied. Physicochemical properties for solid dispersions were investigated using Fourier transform infrared analysis, differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, and scanning electron microscopy. The solubility of the prepared solid dispersions increased except for those prepared with Soluplus® using supercritical fluid technology without co-solvent. The best enhancement in the release profile was recorded by Soluplus®-based solid dispersions prepared using a conventional method. The conventional methods of preparation and the presence of co-solvent in supercritical fluid technology converted cefixime into its amorphous form.

Investigation of Carrageenan Aerogel Microparticles as a Potential Drug Carrier.

Carrageenan is an anionic polysaccharide offering many advantages to be used in drug delivery applications. These include availability, thermo-stability, low toxicity, and encapsulating properties. Combination of these properties with aerogel properties like large surface area and porosity make them an ideal candidate for drug adsorption and delivery applications. Emulsion-gelation technique was used to prepare carrageenan gel microparticles with supercritical CO2 for drying and loading purposes. Ibuprofen has been selected as a model drug for drug loading inside. The prepared microparticles were characterized using particle size analysis, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, density measurements, surface area, and porosity measurements. Finally, dissolution was applied to the loaded preparations to test in vitro drug release. Ibuprofen was successfully loaded in the amorphous form inside the prepared microparticles with a significant enhancement in the drug release profile. In conclusion, prepared carrageenan aerogel microparticles showed an excellent potential for use as a drug carrier.

Significant solubility of carbon dioxide in Soluplus® facilitates impregnation of ibuprofen using supercritical fluid technology.

Treatment of Soluplus® with supercritical carbon dioxide allows promising applications in preparing dispersions of amorphous solids. Several characterization techniques were employed to reveal this effect, including CO2 gas sorption under high pressure and physicochemical characterizations techniques. A gravimetric method was used to determine the solubility of carbon dioxide in the polymer at elevated pressure. The following physicochemical characterizations were used: thermal analysis, X-ray diffraction, Fourier transform, infrared spectroscopy and scanning electron microscopy. Drug loading of the polymer with ibuprofen as a model drug was also investigated. The proposed treatment with supercritical carbon dioxide allows to prepare solid solutions of Soluplus® in less than two hours at temperatures that do not exceed 45 °C, which is a great advantage to be used for thermolabile drugs. The advantages of using this technology for Soluplus® formulations lies behind the high sorption capability of carbon dioxide inside the polymer. This will ensure rapid diffusion of the dissolved/dispersed drug inside the polymer under process conditions and rapid precipitation of the drug in the amorphous form during depressurization accompanied by foaming of the polymer.