Background: Captopril (CAP), an angiotensin-converting enzyme inhibitor (ACEI), is widely prescribed for managing hypertension, heart failure, and related conditions. When administered orally, CAP undergoes hepatic metabolism, resulting in a bioavailability of 60–75%. However, to bypass the first-pass metabolism and other limitations of the oral route, mucoadhesive buccal films have gained attention as a promising alternative with several advantages. The aim of this work was the formulation and optimization of chitosan-ascorbate mucoadhesive films for buccal delivery of CAP for the management of a hypertension crisis (10 mg and 20 mg) by employing quality by design (QbD) principles and the design of experiment (DoE) approach. Materials and methods: In the present work, chitosan (CHI) was selected as a film-forming agent due to its permeability-enhancing properties, which could be further improved through salification with ascorbic acid (AA). The polymer films were prepared by the solvent casting method. Results: The optimized CAP-loaded formula showed appropriate in vitro mucoadhesion force (>15 N) and breaking hardness (>14 N). The different CAP-containing films had a high drug content (>95%) with homogeneous drug distribution, thus complying with the requirements of Pharmacopeia. FT-IR and RAMAN spectroscopy analyses demonstrated successful incorporation of the drug, and interaction was observed between the excipients of the films, especially in the form of hydrogen bonds. The dissolution test showed immediate release of the API with a similar release pattern from both concentrations of CAP-loaded films. Conclusions: The properties of the prepared films met the predetermined critical quality attribute requirements. The optimized formula of CHI 1.4%, AA 2.5%, and glycerol 0.3% appears to be a promising buccal drug delivery system for CAP.
30 May 2022 in Research Journal of Pharmacy and Technology
Carteolol HCl (CRT) is a non-selective beta blocker used to treat glaucoma. Currently, it is delivered via eye drop solutions, which suffer from many limitations (e.g. low bioavailability, high dose requirements and noncompliance). Contact lenses are used by scientists to control the release of ocular drugs, and they are considered as a promising therapeutic tool. This research aimed to evaluate the effect of oleic acid (OA) incorporation on CRT loading and its release from commercial silicone contact lens using the soaking method. Two different concentrations of oleic acid solution (35 and 60mg/ml) and one concentration of CRT solution (2 mg/ml) were used. Drug release profile and various lens properties including changes in visible light transmittance, water content, lens diameter and tensile modulus were investigated. The two used concentrations of oleic acid solution (35 and 60mg/ml) led to oleic acid loadings of 14.6% and 24% respectively, which in turn enhanced the total amount of released CRT by a factor of about 10 and 18, and increased the 90% drug release time by a factor of about 12 and 56, respectively for AIR OPTIX® lens. As for the characterization of prepared lenses, all the results were acceptable compared with unmodified lenses except for the change in diameter of lenses loaded with 24% of oleic acid. Our findings revealed the potential of using oleic acid to improve the uptake of CRT and to achieve sustained release kinetics without compromising the critical properties of contact lens.