Preparation Of Solid Dispersions Research Articles

Sweeteners Show a Plasticizing Effect on PVP K30-A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions.

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer-excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer.

Third Generation Solid Dispersion-Based Formulation of Novel Anti-Tubercular Agent Exhibited Improvementin Solubility, Dissolution and Biological Activity.

The long treatment period and development of drug resistance in tuberculosis (TB) necessitates the discovery of new anti-tubercular agents. The drug discovery program of the institute leads to the development of an anti-tubercular lead (IIIM-019), which is an analogue of nitrodihydroimidazooxazole and exhibited promising anti-tubercular action. However, IIIM-019 displays poor aqueous solubility (1.2µg/mL), which demands suitable dosage form for its efficient oral administration. In the present study, third generation solid dispersion-based formulation was developed to increase the solubility and dissolution of IIIM-019. The solubility profile of IIIM-019 using various polymeric carriers was determined and subsequently, PVP K-30 and P-407 were selected for preparation of binary and ternary solid dispersion. The third-generation ternary solid dispersion comprising PVP K-30 and P-407 revealed a remarkable enhancement in the aqueous solubility of IIIM-019. Physicochemical characterization of the developed formulations was done by employing FTIR spectroscopy, scanning electron microscopy, X-ray diffraction analysis, differential scanning calorimetry, and dynamic light scattering analysis. The dissolution study indicated an impressive release profile with the optimized formulation. The optimized formulation was further examined for cytotoxicity, cellular uptake, and hemolytic activity. The results indicated that the formulation had no apparent cytotoxicity on Caco-2 cells and was non-hemolytic in nature. Moreover, the optimized formulation showed significantly improved anti-tubercular activity compared to the native molecule. These findings showed that the developed third generation ternary solid dispersion could be a promising option for the oral delivery of investigated anti-tubercular molecule.

Preparation and evaluation of naproxen ternary solid dispersion using genetically modified cassava starch and hydroxypropyl methyl cellulose

Background: Naproxen has poor aqueous solubility and high permeability, making its formulation into oral dosage form challenging. The objective of this work was to enhance naproxen aqueous solubility by formulating it into solid dispersion (SD) using genetically modified cassava starch (GMCS) and hydroxypropyl methyl cellulose (HPMC) as polymers, and polysorbate-80 as surfactant.Materials and Methods: Naproxen SD was prepared by solvent evaporation. Different polymer-drug ratios (1:1, 2:1, 3:1 and 4:1) were used. The SDs were evaluated for solubility and the optimum formulation (S2) subjected to Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Pure naproxen tablets (TN) and S2 tablets (T2) were directly compressed and assessed for hardness, friability, weight uniformity, disintegration and dissolution times.Results: The SD of polymer/drug ratio 2:1 and GMCS/HPMC proportion 2:1 had the highest solubility with the polymers showing synergism. Incorporating polysorbate-80 improved solubility by over 20 folds. SEM micrograph of the SD appeared smooth and spherical. DSC thermogram indicated a reduction in crystallinity of naproxen. FTIR spectrum showed no evidence of interaction with the polymers. T2 and TN tablets showed acceptable hardness, disintegration time and weight uniformity. The t50 and t90 dissolution values for T2 were 4.9 and 37.7 minutes respectively which were considerably lower than that of TN (28.57 and 63.42 minutes).Conclusion: Naproxen solubility was enhanced by solid dispersion formulation using genetically-modified cassava starch/HPMC blend. Synergistic effect in the improvement of naproxen solubility was established between the polymers. Inclusion of polysorbate-80 also improved naproxen solubility in the solid dispersion.

Preparation and characterisation of kaempferol composite carrier solid dispersion: evaluation of its application in preventing soybean oil spoilage

Kaempferol (KPF) can be used as a natural antioxidant and food additive in food processing. However, the poor solubility of KPF limited its bioavailability and application. In order to improve the solubility of KPF, kaempferol composite carrier solid dispersion (KPF-CC-SD) was prepared and the process was optimised. When the ratio of KPF: CA (citric acid): Soluplus reached 1:4:6, the dissolution rate was the highest, and the sample was stable over 12 weeks. The characterisation results indicated that KPF-CC-SD exists in an amorphous form. Peroxidation value and acid value of soybean oil showed that the preservation effect of KPF-CC-SD was better than that of KPF, and the inhibition effect of KPF-CC-SD on acid value was better than that of butylated hydroxytoluene. In conclusion, KPF-CC-SD can change the solubility, crystal form and spatial stability of KPF through the carrier, which has a great application prospect in the field of food preservation.

Hydrolysis of Cellulose Acetate Phthalate and Hydroxypropyl Methylcellulose Phthalate in Amorphous Solid Dispersions

The preparation of amorphous solid dispersions (ASDs) represents a promising strategy for addressing the solubility limitations of poorly soluble drugs, facilitating enhanced absorption. Acidic polymers such as cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose phthalate (HPMCP) have emerged as effective carriers for ASDs. Although the hydrolytic degradation of these polymers has been documented, its impact on the stability of ASDs has not been systematically investigated. This research aimed to explore the potential hydrolysis of CAP and HPMCP and how it influences the stability of ASDs containing ketoconazole (KTZ), at drug loadings of 10 % and 50 %. Our study utilized thermal analysis, infrared spectroscopy, and evaluations of physical and chemical stability. The results revealed that although KTZ remained physically stable in all ASDs over a 60-day period under various stability conditions, the emergence of crystalline phthalic acid (PA), a byproduct of polymer hydrolysis, was observed at elevated temperatures and relative humidity levels. The acidic microenvironment fostered by the release of PA further catalyzed drug chemical degradation. This study underscores the susceptibility of CAP and HPMCP to hydrolytic degradation, highlighting the inherent risk of PA-induced drug degradation, particularly for acid-labile compounds. These insights into the understanding of polymer hydrolysis in ASDs pave the way for the development of targeted approaches to safeguard drug stability and optimize pharmaceutical formulations for enhanced bioavailability, efficacy, and safety.

Ternary solid dispersions of lacidipine: Enhancing dissolution and supersaturation maintenance through strategic formulation optimization

The study aimed to address the challenges related to insufficient dissolution and maintenance of supersaturation in binary solid dispersions. Lacidipine, categorized as a BCS class II drug, was employed as the model drug. A systematic screening of excipients was conducted to determine the most effective carriers for the formulations of the ternary solid dispersions, utilizing the solvent transfer method and equilibrium solubility measurements. Both binary and ternary solid dispersions were prepared via spray drying, and comprehensive physicochemical characterization confirmed the successful preparation of amorphous solid dispersions. In vitro dissolution tests, the ternary solid dispersion exhibited marked superiority over the binary solid dispersion in dissolution and maintenance of supersaturation. Furthermore, an exploration into the factors influencing the stability of ternary solid dispersions revealed their robust resistance under light-protected, room-temperature, and desiccated conditions. The formation of intermolecular hydrogen bonding within the molecules of the ternary solid dispersions significantly enhanced drug solubility and system stability. Strategic formulation optimization, coupled with judicious selection of suitable carrier types and ratios, may serve as a promising approach for designing supersaturated drug delivery systems.

Formulation and characterization of glipizide solid dosage form with enhanced solubility.

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

Screening of Organic Small Molecule Excipients on Ternary Solid Dispersions Based on Miscibility and Hydrogen Bonding Analysis: Experiments and Molecular Simulation.

The preparation of solid dispersions by mixing insoluble drugs with polymers is the main way to improve the aqueous solubility of drugs. The introduction of organic small molecule excipients into binary solid dispersions is expected to further enhance drug solubility by regulating intermolecular hydrogen bonding within the system at the microscopic level. In this study, we used carbamazepine (CBZ) as the target drug and polyvinylpyrrolidone as the solid dispersion matrix and screened the third component from 13 organic small molecules with good miscibility in the solid dispersion based on the principle of similarity of solubility parameters. The hydrogen bonding parameters and dissociation Gibbs free energy of the 13 organic small molecule-CBZ dimer were calculated by quantum mechanical simulation, and the tryptophan (Try) was identified as the optimal third component of organic small molecule. The migration of CBZ in binary and ternary systems was also analyzed by molecular dynamics simulation. On this theoretical basis, the corresponding solid dispersions were prepared, characterized, and tested for solubility analysis, which verified that the drug solubility was stronger for the system with the addition of polar fractions and the Try was indeed the best third component of organic small molecule compound, which was consistent with the simulation predictions. This screening method may provide theoretical guidance for drug modification design and clinical studies.

Preparation and Evaluation of Telmisartan Solid Dispersion as Sublingual Tablets

Background: Telmisartan is an antihypertensive angiotensin II receptor antagonist drug commonly used to treat hypertension and renal disease. Based on the Biopharmaceutical Classification System. It’s a Class II poorly soluble drug. Objective: To prepare a sublingual tablet by increasing the dissolution and solubility of Telmisartan utilizing the solid dispersion method. Methods: Three methods were obtained to prepare the solid dispersion of telmisartan: solvent evaporation, Kneading, and microwave method. Each method uses surplus as a hydrophilic carrier in different ratios of 1%, 2%, and 3%. Preparation of ternary solid dispersion by adding potassium carbonate salt to the binary solid dispersion. After that preparing the sublingual tablets by applying a direct compression method, using different types and ratios of superdisintegrants such as crospovidone, croscarmellose and sodium starch glycolate in 5% and 10%. Study the evaluation tests of sublingual tablets, such as friability, hardness, disintegration time and dissolution time. Results: The solid dispersion showed an improvement in solubility over the pure medication. The best result was obtained with the formula (Telmisartan, soluplus and k2co3 salt at 1:1:0.3 ratio) prepared by microwave method, in this method and the high ratio of soluplus, the solubility increased more than the solvent evaporation and kneading method. The selected tablet is prepared using crospovidone 10% as a superdisintegrant that appears disintegration time in 5 seconds and releases in 1 min in dissolution media. Conclusion: The solubility and dissolution of Telmisartan were improved by microwave-based ternary solid dispersion using hydrophilic carriers and salt in a ratio of 1:1:0.3 (drug: carrier: salt). The analysis exerts the increases in wettability, enhanced solubility, and dissolution due to conversion from crystal to amorphous state. Received May. 2023 Accepted Aug. 2023 Published Jan. 2024

One-Step Preparation of Fiber-Based Chlorzoxazone Solid Dispersion by Centrifugal Spinning.

An amorphous fiber-based solid dispersion of chlorzoxazone was prepared for the first time by employing centrifugal spinning, using polyvinylpyrrolidone as the fiber-forming polymer. After optimization of the spinning parameters, the obtained fibers were characterized using a set of analytical techniques, both in a solid- and solution-state. Morphological characterization revealed a slightly aligned, defect-free fibrous structure with an average fiber diameter of d = 3.07 ± 1.32 μm. The differential scanning calorimetric results indicated a crystalline-to-amorphous transition of the active substance during the centrifugal spinning process, while gas chromatographic determinations revealed a residual ethanol content of 0.42 ± 0.04%. UV spectroscopy indicated the incorporation of chlorzoxazone in the fibrous structures, with an average active substance content of 15.91 ± 0.36 w/w%. During small-volume dissolution studies, the prepared fiber mats presented immediate disintegration upon contact with the dissolution media, followed by rapid dissolution of the active substance, with 84.8% dissolved at 1 min and 93.7% at 3 min, outperforming the micronized, pure chlorzoxazone. The obtained results indicate that centrifugal spinning is a low-cost, high-yield, viable alternative to the currently used methods to prepare fiber-based amorphous solid dispersions of poorly soluble drugs. The prepared chlorzoxazone-loaded microfibers could be used as a buccal dosage form for the systematic delivery of chlorzoxazone and could potentially lead to a rapid onset of action and longer efficacy of the muscle relaxant drug.

Design, Development and in Vitro Characterization of Emulgels Loaded with Fluconazole Solid Dispersion and Various Oils for Synergestic Anti-Fungal Effect

Topical Fungal Infections are the most common types of skin infections. Nearly a billion people are suffering from fungal infections of different types. Early accurate diagnosis and treatments may lead to complete cure of such infections, which if left untreated may lead to deadly results. Our current Research topic includes designing of antifungal emulgels that contain oil base which already has proven its efficacy against fungal infections and Fluconazole as the main active ingredients. Three oils were selected namely Tea tree oil, Neem oil and Lemon grass oil. To enhance the efficacy of BCS class II drug fluconazole, solid dispersions of the drug were prepared(F1-F6). Twelve formulations (EGF1-EGF12) containing various combination of oils, gelling agents, API, Aloe vera gel were prepared. Which were then evaluated and characterized for properties like drug content, Rheological study, spread ability, Drug release, pH, stability analysis etc. Among all the formulations EGF2 and EGF5 showed optimum results for drug content and drug release kinetics. The Best selected formulations were then compared with marketed gel formulation of Fluconazole and were kept for stability study analysis. Preformulation studies of the drug, preparation of solid dispersions, incorporation of these solid dispersions into emulgels and characterization of prepared emulgels by comparing with marketed formulations are the main key points of our Research work.

Hot "Dissolving" Extrusion of Lurasidone with Natural Liquid Small Molecule for Amorphous Solid Dispersion Based Self-Assembled Submicron Emulsion.

Nowadays, ≈90% of new drug candidates under development are poorly bioavailable due to their low solubility and/or permeability. Herein, a natural liquid small molecule trans-anethole (TA) is introduced into the drug-polymer system lurasidone (LUS)-poly (1-vinylpyrrolidone-co-vinyl acetate) (VA64), notably improving the compatibility of components for the successful preparation of amorphous solid dispersion (ASD) and facilitating the formation of self-emulsifying drug delivery system (SEDDS) during dissolution. LUS-TA-VA64 ASD shows enhanced supersaturation with a long maintenance time of at least 24 h over pure LUS. The strong non-covalent force between VA64 (as emulsifier) and TA (as oil phase)/ water promotes the self-assembly of submicron emulsion and ensures its stability for at least 10 h. Compared to the commercial salt form of LUS, the ASD shows twofold increase in peak plasma concentration (Cmax ) and area under plasma concentration-time profiles (AUC), 1.5-fold increase in peak time (Tmax ), and twofold decrease in AUC-based coefficient of variation (CV) (59%→26%) after a single oral dose to a rabbit.

Formulation and in vitro /in vivo Evaluation of Silymarin Solid Dispersion- Based Topical Gel for Wound Healing

Silybum marianum, from which silymarin (SM) is extracted, is a medicinal herb. In the Biopharmaceutics Classification System, it is of the class II type, meaning it is almost completely insoluble in water. It has a number of therapeutic properties, including anti-inflammatory as well as properties that promote wound healing. This research target is to promote the dissolution and solubility of SM by employing a technique called solid dispersion and then incorporating the formula of solid dispersion into a topical gel that can be used for wound healing. Solid dispersion is a technique used to enhance solubility and dissolve pharmaceuticals that are not water-soluble. This method is widely used because of its low cost and high efficiency. Because of its capacity to repair skin, the hydrophilic carrier nicotinamide (NA) was selected in this investigation as the carrier. Kneading, solvent evaporation and fusion with a consistent drug-to-carrier ratio were the three separate processes utilized in the preparation of solid dispersion (1:1, 1:3, and 1:5). In addition, the products were examined to determine their physical characteristics and the degree of crystallinity. The selected formula was combined into a hyaluronic acid base gel using the cold method. This gel was then evaluated in vitro for physical qualities and put to an in vivo (animal) examination to determine how it healed wounds. The study found that the solvent evaporation made SM 25 times more soluble and caused all of it to be released in 20 minutes for a 1:3 ratio. Additional research using DSC and XRD demonstrated the amorphous nature of the result. According to FTIR, there was no evidence of interaction between the two. The gel formula had good qualities, like a pH of 6.6, good spreadability, and drug release within three hours. It also contributed to the rapid healing of wounds.

Solubility and Physical Stability Enhancement of Loratadine by Preparation of Co-Amorphous Solid Dispersion with Chlorpheniramine and Polyvinylpyrrolidone.

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization.

Preparation and Characterization of Carvedilol Solid Dispersion by Kneading Method

Solid dispersion using hydrophilic carrier is one of the approaches that has a potential to increase solubility, dissolution rate and consequently the oral bioavailability of poorly-water soluble drugs. In this study, class II drug "Carvedilol" (CVD) was used because of its poor solubility, it serves as a model drug that contributes to irregular dissolution and limited bioavailability. CVD: PVP K30 solid dispersion formulations SD1, SD2 and SD3 were prepared by kneading method at different weight ratios ,1:1; 1:2 and 1:4 respectively and evaluated for drug content, solubility and dissolution rate. Kneading method enhances the stability of drugs and suitable for processing thermolabile substances. The optimum solid dispersion ratio was characterized also for drug-carrier interaction by FTIR spectroscopy, and crystallinity by SEM and PXRD and compared with physical mixture and pure drug powder.
 The results showed that the solubility of carvedilol increased by increasing the proportion of PVP K30 used in the dispersion of the drug. On the other hand, dissolution study revealed a significant enhancement in the dissolution rate of the drug using solid dispersion compared to pure drug and physical mixture. X-ray diffraction of the solid dispersion suggest that the drug's transformation from crystalline to amorphous form may be responsible for the observed improvement in dissolving rate. The carvedilol solid dispersion improved the solubility and dissolution, which depend on the carrier concentration ratio. The dissolution of drugs increased with an increase in carrier content. The studies of PXRD, SEM, and FTIR revealed the amorphous nature of the drug in solid dispersion. The solid dispersion by kneading approach using PVP K30 as a carrier is a potential method for improving CVD's solubility and dissolution rate.

Screening and optimization of supercritical fluid process for the preparation of albendazole solid dispersion

Screening and optimization of supercritical fluid process for the preparation of albendazole solid dispersion

Preparation of solid dispersion of Dushen decoction and establishment of its evaluation method

Preparation of solid dispersion of Dushen decoction and establishment of its evaluation method

Preparation and Characterization of Spray-Dried Hybrid Nanocrystal-Amorphous Solid Dispersions (HyNASDs) for Supersaturation Enhancement of a Slowly Crystallizing Drug.

We prepared hybrid nanocrystal-amorphous solid dispersions (HyNASDs) to examine their supersaturation capability in the release of a poorly soluble drug, itraconazole (ITZ), a slow crystallizer during dissolution. The HyNASD formulations included a polymer (HPC: hydroxypropyl cellulose, Sol: Soluplus, or VA64: Kollidon-VA64) and a surfactant (SDS: sodium dodecyl sulfate). Additionally, the dissolution performance of the HyNASDs and ASDs was compared. To this end, wet-milled aqueous nanosuspensions containing a 1:5 ITZ:polymer mass ratio with/without SDS as well as solutions of the same ratio without SDS in dichloromethane were spray-dried. XRPD-DSC confirmed that ASDs were formed upon spray drying the solution-based feeds, whereas HyNASDs (~5-30% amorphous) were formed with the nanosuspension-based feeds. SDS aided to stabilize the ITZ nanosuspensions and increase the amorphous content in the spray-dried powders. During dissolution, up to 850% and 790% relative supersaturation values were attained by HyNASDs with and without SDS, respectively. Due to the stronger molecular interaction between ITZ-Sol than ITZ-HPC/VA64 and micellar solubilization by Sol, Sol-based HyNASDs outperformed HPC/VA64-based HyNASDs. While the ASD formulations generated greater supersaturation values (≤1670%) than HyNASDs (≤790%), this extent of supersaturation from a largely nanocrystalline formulation (HyNASD) has not been achieved before. Overall, HyNASDs could boost drug release from nanoparticle-based formulations and may render them competitive to ASDs.

Increase of solubility and transmembrane permeability of niclosamide from its mechanochemically synthesized solid dispersions

More than 4.5 billion people worldwide are affected by parasitic diseases, with helminth infections accounting for 99% of the total number. Niclosamide (NS) is a weakly acidic active pharmaceutical ingredient (API) used to treat helminth infections. However, the pharmaceutical use of pure niclosamide is limited by its low bioavailability due to its poor aqueous solubility. The aim of this work is a mechanochemical preparation of niclosamide solid dispersions with increased solubility. Due to the pH dependence of NS water solubility and possible complexes formation, NS solid dispersions (SD) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and alkalizing agents, such as calcium carbonate (CaCO3) and N-methyl-D-glucamine (MG) are mechanochemically prepared in this study. The physical properties of NS SD in solid state are characterized by differential scanning calorimetry, X-ray diffraction, FT-IR spectroscopy, and scanning electron microscopy studies. The characteristics of the water solutions formed from the obtained SDs are analyzed by HPLC. It is shown that the solubility increases for all studied compositions. These phenomena are obliged by complexation with HP-β-CD, which was shown by 1H-NMR methods, and enhanced ionization in the cases of using calcium carbonate and MG. Results of the parallel artificial membrane permeability assay (PAMPA) have shown that mechanochemically obtained NS/MG SD (1/1 mass ratio, 8 h milling) significantly enhances permeation of NS across an artificial membrane. Thus, the obtained compositions are a promising basis for the development of NS-based preparations for oral administration, with reduced dose and high pharmacological effect.

Supercritical fluid (SCF)-assisted preparation of cyclodextrin-based poly(pseudo)rotaxanes for transdermal purposes

This study aims to investigate the effect of the preparation of solid dispersions using supercritical CO2 (scCO2) on the physicochemical properties and the performance of supramolecular gels based on polymer-cyclodextrin (CD) interactions (named poly(pseudo)rotaxanes, PPR) envisaging a transdermal administration. Solid dispersions containing Soluplus®, the antihypertensive drug carvedilol (CAR), and CD (αCD or HPβCD) were prepared and characterized by HPLC, XRPD, FTIR, and DSC. PPRs prepared from solid dispersions (SCF gels) and the corresponding physical mixtures (PM gels) were analyzed regarding rheology, morphology, in vitro drug diffusion, and ex vivo drug skin permeation. The application of scCO2 led to the loss of the crystalline lattice of CAR while preserving its chemical identity. On the contrary, αCD crystals were still present in the SCF solid dispersions. SCF gels were more uniform than their corresponding PM, and the supercritical treatment resulted in changes in the rheological behavior, reducing the viscosity. CAR in vitro diffusion was significantly higher (p < 0.05) for the αCD-based SCF gel than its corresponding PM gel. Drug skin permeation showed a significant increase in drug flux from CD-based SCF gels (containing αCD or HPβCD) compared to corresponding PM gels. Additionally, the pretreatment of the skin with αCD exhibited increased CAR permeation, suggesting an interaction between αCD and the skin membrane. Results evidenced that SCF processing decisively modified the properties of the supramolecular gels, particularly those prepared with αCD.Graphical