Optimized Formulation of Carvedilol Fast-Dissolving Tablets Using Modified Super disintegrants: Breaking Solubility Barriers of BCS Class II Drugs
Indian Journal of Pharmaceutical Education and Research
Abstract
Background: The BCS Class-II faces major challenge, low solubility and poor bioavailability issues. Carvedilol, an anti-hypertensive drugs, has a bioavailability 20-25%. Objectives: This research focuses on the development of fast dissolving tablets for Carvedilol (CARV), utilizing sorghum starch modified with humic acid as a novel superdisintegrant through factorial design to achieve rapid drug dissolution, bioavailability and patient compliance. Materials and Methods: Sorghum starch was isolated through a modified alkaline treating method from sorghum flour then it was modified with humic acid to form starch humate. Various tests such as gelatinization, viscosity, pH and flowability were performed. Quality by design was applied to identify the most important characteristics (response variables) such as disintegration time, dissolution efficiency and cumulative percent drug dissolved at the end of 10 min. The independent variables are starch humate, sodium starch glycolate and crospovidone. The direct compression approach was used to develop carvedilol fast dissolving tablets with a 23-factorial design. The formulations were assessed for flow characteristics, drug compatibility using FTIR, DSC and XRD, morphology using a scanning electron microscope, amount of drug, in vitro and in vivo drug release profiles and stability. Results: The modified starch-starch humate has a higher viscosity, pH value, and better flowability than sorghum starch. FTIR and DSC investigations revealed no interaction with the drug and the superdisintegrants. Optimized CARV-FDTs with 5% starch humate demonstrated adequate friability (0.59±0.68%), disintegration time (28±0.02 sec), % PD10 (98.40±0.64%), wetting time (22±0.36 sec), water absorption ratio (68±1.41) and DE (70.9±0.34). They also demonstrated satisfactory stability under accelerated conditions along with improved relative bioavailability, reaching the highest plasma concentration in a short time. Conclusion: This study discovered that modified starch humate can potentially be extracted and developed into fast dissolving tablets by QbD in the management of hypertension exhibiting enhanced relative bioavailability and patient acceptance.
Keywords
- Bioavailability
- Fast Dissolving Tablets
- Sorghum starch
- Starch humate
- Superdisintegrant