In vitro evaluation of extemporaneously compounded immediate-release capsules with premixed excipients, based on the biopharmaceutics classification system (BCS) of the drugs

Abstract

Hard-capsule compounding plays an essential role in drug delivery for pharmaceutical application. Versatile and easy to use, capsules represent a popular dosage form for patients. Nevertheless, bioavailability of the drugs compounded in hard capsules is not always optimized and choosing the appropriate excipients is a key factor to improve the dissolution kinetics of active pharmaceutical ingredients. The Biopharmaceutical Classification System, which categorizes drugs regarding their solubility and permeability, is a unique tool which can be used to select the most compatible excipients for a particular drug when compounding immediate-release capsules. The aim of this study was to evaluate the efficiency of premixed excipient blends called CapsuBlend Excipients, based on the Biopharmaceutical Classification System concept, for drug dissolution rate and absorption enhancement. Drug assay and dissolution profiles were studied for three batches of metronidazole 250-mg, theophylline 100-mg, and levocarnitine 250-mg capsules, each respectively representing a highly soluble, poorly soluble, and hygroscopic drug. Methods followed the specifications set forth in the United States Pharmacopeia. Assay results demonstrated that each batch of metronidazole 250 mg, theophylline 100 mg, and levocarnitine 250 mg contained not less than 90.0% of and not more than 110.0% of the labeled amount of drug, which is in accordance with the United States Pharmacopeia requirements. Moreover, dissolution profile results for the aforementioned capsules depicted dissolution values meeting the Pharmacopeial criteria of acceptance. These results reinforce the fact that the Biopharmaceutical Classification System concept represents a valuable guideline for formulation chemists or pharmacists to assist them for capsule compounding. To ensure a high level of efficiency of compounded capsules, premixed excipient blends, carefully developed by taking into consideration the solubility and permeability of a drug, represent a significant formulation advantage to improve the dissolution of active pharmaceutical ingredients.