Effect of Hydrophilic Carriers for Solubility and Dissolution Enhancement of Sulfamerazine by Solid Dispersions Technique

Aims: The present research was carried out to investigate the effect of hydrophilic carriers in enhancing the solubility and dissolution rate of Sulfamerazine (SMZ) employing the fusion technique of solid dispersions (SD). Methodology: SMZ is an oral antibacterial drug exhibiting a poor dissolution profile and water solubility. SD of SMZ was prepared using poloxamer 407 (PX407) and Polyethylene glycol 6000 (PEG6000) as a hydrophilic carrier by employing the fusion technique. Results: The powder SDs were subjected for solubility, Fourier transform infrared spectrometry (FTIR), Differential scanning calorimetry (DSC), in-vitro dissolution profile, Scanning electron microscopy (SEM), and X-ray diffraction (XRD) study. The FTIR spectral analysis showed no significant incompatibility between drug and carriers and confirmed the presence of SMZ. From XRD and DSC, SMZ indicated the amorphous form in solid dispersion with larger specific surface area, resulting in a better in-vitro rate of dissolution of the drug from solid dispersions than pure drug. However, SD of PX407 (SDSMFF8) indicated higher aqueous solubility than pure SMZ. Further, SDSMFF7 showed higher in-vitro drug release 96.45±0.3% within 60 minutes, and pure drug (18.54±0.8%). Conclusion: In conclusion, enhancing thesolubility and dissolution of SMZ using hydrophilic carriers by solid dispersion technique provides new strategies for broadening its potential clinical application.

The Promising Role of Chitosan–Poloxamer 188 Nanocrystals in Improving Diosmin Dissolution and Therapeutic Efficacy against Ferrous Sulfate-Induced Hepatic Injury in Rats

Diosmin (DSN) exhibits poor water solubility and low bioavailability. Although nanocrystals (NCs) are successful for improving drug solubility, they may undergo crystal growth. Therefore, DSN NCs were prepared, employing sonoprecipitation utilizing different stabilizers. The optimum stabilizer was combined with chitosan (CS) as an electrostatic stabilizer. NCs based on 0.15% w/v poloxamer 188 (PLX188) as a steric stabilizer and 0.04% w/v CS were selected because they showed the smallest diameter (368.93 ± 0.47 nm) and the highest ζ-potential (+40.43 ± 0.15 mV). Mannitol (1% w/v) hindered NC enlargement on lyophilization. FT-IR negated the chemical interaction of NC components. DSC and XRD were performed to verify the crystalline state. DSN dissolution enhancement was attributed to the nanometric rod-shaped NCs, the high surface area, and the improved wettability. CS insolubility and its diffusion layer may explain controlled DSN release from CS-PLX188 NCs. CS-PLX188 NCs were more stable than PLX188 NCs, suggesting the significance of the combined electrostatic and steric stabilization strategies. The superiority of CS-PLX188 NCs was indicated by the significantly regulated biomarkers, pathological alterations, and inducible nitric oxide synthase (iNOS) expression of the hepatic tissue compared to DSN suspension and PLX188 NCs. Permeation, mucoadhesion, and cellular uptake enhancement by CS may explain this superiority.

Effect of Amphiphilic Graft Co-Polymer Carrier on Solubility and Dissolution Enhancement of Ambrisentan

Aim: Ambrisentan is a endothelin type A selective receptor antagonist used in the management of pulmonary arterial hypertension. Ambrisentan is BCS Class II drug haves very poor solubility in water and shows incomplete absorption after oral administration. The present work was aimed to study the effect of amphiphilic graft co-polymer carrier on enhancement of solubility and dissolution rate of poorly water soluble drug ambrisentan. To improve the aqueous solubility of ambrisentan solid dispersion was formulated by using novel carrier amphiphilic graft co-polymer (Soluplus® ). Materials and Methods: Solid dispersion was prepared by kneading technique by utilizing various ratios of carrier. Obtained solid dispersions ware evaluated for solubility, percentage yield, drug content and in vitro dissolution study. Powder characterization was performed by infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Results: FTIR spectroscopy shows no interaction between drug and polymer. DSC study showed that endothermic peak of drug was completely disappeared in Solid dispersion suggesting complete miscibility of drug in Soluplus®. XRD study suggest the conversion of crystalline ambrisentan in to amorphous form. All solid dispersions prepared with Soluplus® as a carrier showed increase in solubility. Solubility of ambrisentan was found to be increased 7.17 fold in optimized SD formulation ASD5. In vitro dissolution study showed the faster drug release from SD formulation compare to its pure form. All solid dispersion formulation’s release more than 50% of drug in first 10 min. Conclusion: This study conclude that the preparation of amphiphilic graft co-polymer based solid dispersion prepared by kneading technique is found to be useful in enhancement the solubility and dissolution rate of ambrisentan.

Effect of Surfactants and Polymers on the Dissolution Behavior of Supersaturable Tecovirimat-4-Hydroxybenzoic Acid Cocrystals

(1) Background: Pharmaceutical cocrystals have attracted remarkable interest and have been successfully used to enhance the absorption of poorly water-soluble drugs. However, supersaturable cocrystals are sometimes thermodynamically unstable, and the solubility advantages present a risk of precipitation because of the solution-mediated phase transformation (SMPT). Additives such as surfactants and polymers could sustain the supersaturation state successfully, but the effect needs insightful understanding. The aim of the present study was to investigate the roles of surfactants and polymers in the dissolution-supersaturation-precipitation (DSP) behavior of cocrystals. (2) Methods: Five surfactants (SDS, Poloxamer 188, Poloxamer 407, Cremophor RH 40, polysorbate 80) and five polymers (PVP K30, PVPVA 64, HPC, HPMC E5, CMC-Na) were selected as additives. Tecovirimat-4-hydroxybenzoic (TEC-HBA) cocrystals were chosen as a model cocrystal. The TEC-HBA cocrystals were first designed and verified by PXRD, DSC, SEM, and FTIR. The effects of surfactants and polymers on the solubility and dissolution of TEC-HBA cocrystals under sink and nonsink conditions were then investigated. (3) Results: Both the surfactants and polymers showed significant dissolution enhancement effects, and most of the polymers were more effective than the surfactants, according to the longer Tmax and higher Cmax. These results demonstrate that the dissolution behavior of cocrystals might be achieved by the maintained supersaturation effect of the additives. Interestingly, we found a linear relationship between the solubility and Cmax of the dissolution curve for surfactants, while no similar phenomena were found in solutions with polymer. (4) Conclusions: The present study provides a basis for additive selection and a framework for understanding the behavior of supersaturable cocrystals in solution.