Liquisolid systems: Understanding the impact of drug state (solution or dispersion), nonvolatile solvent and coating material on simvastatin apparent aqueous solubility and flowability.

The drug in a solid dosage form must undergo dissolution before it is available for absorption from the gastrointestinal tract. Liquisolid system (LS) is a technology used for increasing aqueous solubility of the drugs, which has an important role in the dissolution and absorption phenomena. However, many factors can influence the performance and success of LS. Therefore this study aimed to evaluate through a factorial design, the factors such as drug state (solution or dispersion), nonvolatile solvent and coating material that influence the increase simvastatin (BSC II drug) apparent aqueous solubility and LS flow properties. Through numerical optimization the best formulation was selected to develop a liquisolid compact (LC) and it was evaluated by dissolution tests over commercial tablets using two dissolution media. Analyzing the data, the type of nonvolatile solvent and the state of the drug (solution or dispersion) were the factors with the greatest effects on the apparent aqueous solubility response (p < 0.0001 for both). Regarding the responses that evaluated the flow properties, the type of coating material and the type of nonvolatile solvent were the factors that influenced the Carr index (p < 0.0006, p < 0.0023, respectively) and Hausner ratio (p < 0.0006, p < 0.0014, respectively), where formulations containing Kollidon® CL were more efficient than Aerosil® (which is the most commonly used coating material for LS manufacture). These results enabled us to identify which factors were most influential and to move towards the use of new excipients in the case of Kollidon® CL. In addition, allowed a wider evaluation and understanding of LS, which is considered an important technological alternative for the increase of drug solubility.

Ball-milled solid dispersions of BCS Class IV drugs: Impact on the dissolution rate and intestinal permeability of acyclovir.

Acyclovir, an analog of 2'-deoxyguanosine, is one of the most important drugs in the current approved antiviral treatment. However, it's biopharmaceutical properties, contribute to acyclovir's poor oral bioavailability, which restricts the clinical use of the drug. In this view, the aim of this work was to improve the dissolution rate and intestinal permeability of acyclovir through the development of ball milling solid dispersions with the hydrophilic carriers Pluronic F68®, hydroxypropylmethyl cellulose K100M® and chitosan. Solid dispersions were obtained and completely characterized through different solid state techniques. The solid state data demonstrated a decrease in the crystallinity (amorphous phase and defects) and the presence of hydrogen bonds for SD HPMC and SD CTS. The enhancement of dissolution rates was observed for all SDs developed. In addition, no detrimental effects over the in vitro antiviral activity were detected. The solid dispersions with Pluronic F68® significantly improved the intestinal permeability of acyclovir across Caco-2 cells. In summary, the SDs developed in this study could be considered as potential systems for solid dosage forms containing acyclovir with superior biopharmaceutical properties.