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The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs) of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3) SD showed a 36-fold higher solubility of compared with pure ritonavir. Similarly, ritonavir:Kolliphor® P188 (RP, 1:2) SD exhibited a 49-fold higher solubility of ritonavir compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, upto a ritonavir:carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at a ritonavir:Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supporting the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3) and RP (1:2) were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %). A preliminary (six-month) stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that a good solubility, dissolution, and permeability improvement of ritonavir can be achieved with a careful choice of the carrier polymer, and by optimizing the amount of the chosen polymer in an SD formulation. [ABSTRACT FROM AUTHOR]

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics. [ABSTRACT FROM AUTHOR]

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics. [ABSTRACT FROM AUTHOR]

In this study, the feasibility of using pentaerythritol as a novel excipient/solid-dispersion carrier for enhancing the biopharmaceutical properties of ursodeoxycholic acid (UA) is explored. The solid dispersion formulations of UA were prepared using a solvent evaporation technique. The prepared formulations were evaluated for UA content to assess the efficiency of incorporating the UA into the formulation. The formulations were further characterized using photomicroscopy, scanning electron microscopy, particle size analysis, zeta potential analysis, infrared spectroscopy, thermal analysis, x-ray diffractometry, and performing solubility analysis. The performance of the selected formulation was evaluated by dissolution and permeability studies. A preliminary stability study was performed on the selected formulation. Solid dispersions of UA using pentaerythritol as a carrier were successfully prepared using UA providing efficiencies ranging from ~97 to 99%. The formation of dispersions was supported by instrumental analysis. Compared to pure UA, a 22-fold increase in aqueous solubility of UA was observed in the optimized formulation. The biopharmaceutical characteristics of UA, i.e., the rate and extent of dissolution and permeability, were found to be significantly increased in the optimized formulation compared with pure UA. The formulation was also functionally stable for six months when stored at controlled temperatures and humidity. This study shows that pentaerythritol can serve as a potential solid dispersion carrier for active pharmaceutical ingredients (API) and contribute to the enhancement of their biopharmaceutical properties. [ABSTRACT FROM AUTHOR]

A novel quercetin-phospholipid-complex (QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. The QPLC formulation, prepared using a solvent-evaporation method, was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF) or QPLC (QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The films were also functionally characterized for in vitro diffusion of quercetin through a dialysis membrane and ex vivo permeability of quercetin across rat skin. Finally, the anti-inflammatory activity of the films was evaluated on carrageenan-induced paw edema in Wistar albino rats. The experimental design identified the optimal formulation and process variables for the preparation of QPLC. The validation of the obtained model using these values confirmed the suitability and robustness of the model. The physical-chemical characterization of the prepared QPLC supported the formation of a stable complex. The solubility analysis of QPLC showed a 22-fold increase in quercetin aqueous solubility, compared to pure quercetin. The dissolution results exhibited a significantly higher rate and extent of quercetin dissolution from QPLC compared to that of pure quercetin. The permeability of quercetin from Q-MF and QPLC-MF across rat skin mirrored those obtained from the dissolution studies. Topical application of QPLC-MF exhibited a significant (p<0.05) inhibition of carrageenan-induced paw edema in rats compared to that of Q-MF. This study provides a promising combination approach, i.e., phospholipid-based complexation and transdermal film formulation for improved transdermal delivery of quercetin and similar pharmacologically active phytoconstituents. [ABSTRACT FROM AUTHOR]