(M1130-07-39) Revolutionizing Drug Formulations: Delayed Release and Sustained Release Using Hypromellose 2208 Types and Hypromellose Acetate Succinate

Purpose: The purpose of this study is to develop a platform technology for delayed release (DR) and sustained release (SR) formulation to explore the synergistic potential of various grades of Metolose®SR in core tablets, followed by enteric coating using Hypromellose Acetate Succinate (HPMCAS). The project aims to create an advanced pharmaceutical delivery system that offers precise control over drug release kinetics.

Methods: The primary aim of this study was to develop a DR and SR formulation. The formulation process involved two stages, initiating with the optimization of the core tablet using different grades of Metolose® SR i.e. Hypromellose 2208 type and its concentration. The second stage involve the application of an aqueous enteric coating using HPMCAS, followed by a thorough evaluation of the formulation's acid uptake and drug release profile. In this study, Propranolol HCl 80 mg core tablets were formulated using different grades and concentrations of Metolose® SR. Tablet weight is 202 mg with 8mm diameter and 60N tablet hardness. These tablets were then assessed for their dissolution profiles in buffer solutions pH 6.8 to determine the impact of different Metolose® SR grades and concentrations on retarding the drug release profile, ensuring compliance with USP limits. Propranolol core tablets were seal-coated with an aqueous solution of Pharmacoat® 606 for a 3% weight gain. In this seal coating layer, talc was used as an anti-tacking agent, constituting 50% of the polymer weight. The seal-coated tablets were then coated with an aqueous enteric coating polymer, using three grades of HPMCAS for a 7% weight gain. In this enteric coating layer, triacetin was used as plasticizer, SLS was used as wetting agent and talc was used as an anti-tacking agent. The enteric coated tablets were evaluated for acid uptake and their dissolution profiles in acid pH 1.2, followed by a buffer solution pH 6.8 and stability studies.

Results: Propranolol core tablets prepared using various Metolose® SR grades and concentrations were exposed to a pH 6.8 buffer solution, with their drug release profiles depicted in Fig. 01. The drug release profile of enteric-coated tablets for acid protection in pH 1.2 and drug release in pH 6.8 illustrates Fig. 02. The drug release profiles of enteric-coated tablets using different grades of HPMCAS over a one-month stability period shown in Fig. 03.

Conclusion: As core tablets with different Metolose® SR grades were evaluated for drug release in pH 6.8, the results show all Metolose® SR grades successfully retard the drug release. Metolose® 90SH 100000SR (25%) led to release profile which was more towards the lower limit of USP, whereas with Metolose® 90SH 15000SR and Metolose® 90SH 4000SR (25%) the profile was more towards the upper limit of the USP. METOLOSE® 90SH 100000SR with 12% concentration and 15% concentration gave similar release profile. METOLOSE® 90SH 100000SR with 15% concentration was finalized for the further development because the tablet processing was much better when compared with the 12%. For enteric dissolution when compared within the Shin-Etsu AQOAT grades, dissolution of AS-HF complies with USP limit. This is mainly because of the pH solubility of AS-HF which start dissolving at pH 6.8 compared to AS-LF and AS-MF which start dissolving at pH 5.5 and pH 6.0 respectively. On stability the enteric coating tablets were stable as compared with initial drug release profile.

Fig no. 01 Dissolution Profile of Core Tablets at pH 6.8 with Varied Metolose® Grades and Concentrations

Fig no. 02 Drug release from enteric coated tablet at pH 1.2 and pH 6.8 and acid uptake study in pH 1.2

Fig. No. 03 Drug release from Propranolol enteric coated tablets over 1 month stability