Mihir K. Raval and coworkers reported cocrystallization of Albendazole. Cocrystallization approach with solvent evaporation technique at room temperature has been utilized to improve the physicochemical and mechanical properties of albendazole along with its pharmacokinetic parameters.
Cocrystallization of drugs in presence of excipients can become an effective tool to improve physicochemical and mechanical properties of drugs which may ultimately affect its bioavailability and manufacturability. Aim of present investigation was to understand the influence Benzoic acid (BA) on recrystallization behavior of Albendazole (ABZ) using slow (conventional) evaporation technique. Benzoic acid treated crystals showed a unique melting behavior, improved solubility (12.53 folds) and dissolution rate (8.6 folds) with higher drug content (72.17%). Control batch crystals showed a possibility of a new crystalline form with much improved properties. SEM photographs revealed bigger and plate-shaped BA treated crystals with aspect ratio near to unity which improved flow and packability of crystals. Heckel parameters suggested greater plastic deformation and high tensile strength with negligible elastic recovery compared with pure drug. FT-IR studies assumed a formation of hydrogen bond between drug and excipient. Treated crystals were stable even after six months of accelerated stability study. Use of directly compressible excipients could be minimized in the tablet formulation in case of treated crystals. Pharmacokinetic study showed improved (3.42 times) in vivo performance in rats. In this study, improvement in physicomechanical and pharmacokinetic parameters of Albendazole by its cocrystallization could be highlighted.
Fig. 1
Albendazole (ABZ), a member of the benzimidazole family of compounds and is a broad spectrum anthelmintic drug (Fig 1.). Based on powder rheology, albendazole (ABZ) is classified as a powder with poor flow property and compressibility. Besides, albendazole has low aqueous solubility (log P is 13.94) and high permeability (BCS Class II), which limits its oral absorption. Molecular weight of albendazole (ABZ) is 265.33 gm/mol and is weakly basic in nature. Hence, solubility of drug is higher at lower pH rather than at neutral pH. Moreover, the drug has two pKa values of 2.68 and 11.83, respectively. At acidic pH 1.2, the solubility of albendazole (ABZ) is reported 900 μg/ml, whereas at pH above 5, solubility reported was even less than 1 μg/ml. Due to this, albendazole (ABZ) cannot be absorbed completely if not solubilized in the GI tract. Hence, USP has mentioned phosphate buffer pH 1.2 as an official dissolution profile for ABZ tablets.
Raval’s work shows recrystallization of Albendazole (ABZ) in presence of excipient to improve its physicochemical, mechanical as well as pharmacokinetic properties which were major key issues in processing and developing its solid oral dosage form. Various excipients tried for cocrystallization were Cinnamic acid, Benzoic acid, l-Malic acid, Maleic acid, Lauric acid and Myristic acid. Solid-state investigation of prepared crystalline samples is performed to check for generation of new crystal phase of ABZ during cocrystallization. Selection of carboxylic acid moieties as crystallizing excipient is done because of its amenability to form hydrogen bond with API.
Advanced Powder Technology 26 (2015) 1102–1115