(M1430-07-41) Functional Coatings with Cellulose Acetate Grade Combinations in Osmotic Devices – Process Optimization and Release Modulation of Metoprolol Succinate

Purpose: Cellulose acetate (CA) is popularly employed as a functional polymer in designing osmotic drug delivery systems¹. The two grades of cellulose acetate, CA 398-10 NF/EP and CA 320S NF/EP from Eastman chemicals are frequently used either alone or in combination to tailor the release profile². The purpose of the current study was to understand the effect of various combinations of CA 398-10 NF/EP and CA 320S NF/EP (100:0, 90:10, 75:25, 25:75, 50:50 and 0:100) as coating polymer and to evaluate the dissolution profile of Metoprolol succinate under different coating conditions.

Methods: To develop osmotic drug delivery system for Metoprolol succinate using cellulose acetate as coating polymer. The work was divided into the following parts. Part A: Core tablet preparation: Metoprolol succinate granules were prepared using non-aqueous granulation method, using alcoholic Kollidon^® 30 as a binder solution. Briefly, the drug ingredients were added to a rapid mixer granulator along with diluent followed by addition of the binder solution to get the wet mass which under shear produced granules. The granules were further dried using a fluid bed dryer (GPCG 1.1) and passed through sieve #20. Extra-granular ingredients viz., Aerosil^® 200P and Talc were passed through sieve #40 whereas Magnesium stearate was passed through sieve #60 and mixed with granules using double cone blender. Resultant lubricated blend was compressed using 10 mm SC punch to form tablets with a target weight of 353 mg. The tablets were evaluated for IPQC parameters such as weight variation, hardness, friability and disintegration time. Part B: Coating of tablets: The coating solutions were prepared using two cellulose acetate grades CA 398-10 NF/EP and CA 320S NF/EP respectively in different ratios viz, 100:0, 90:10, 75:25, 25:75, 50:50 and 0:100. The polymers were dissolved in acetone/water (90/10) solvent system along with PEG 3350 as a plasticizer (10% of polymer weight) under stirring until a homogenous solution (5% w/w solid content) resulted. The core tablets were coated using Ganscoater (model: GAC 275/250) and the respective cellulose acetate coating solution. Part C: Dissolution profile evaluation: Coated tablets (weight gain: 6%w/w and 9%w/w) were drilled to form an orifice of 0.9 mm diameter and then subjected to in vitro dissolution in 500 mL pH 6.8 phosphate buffer for 20 hours in USP paddle apparatus at 50 rpm at 37degC.

Results: Part A: Core tablet preparation: The fabricated tablets were observed to comply with the weight variation test as per the USP. The hardness of tablets was observed to be in the range of 168 – 194 N. The disintegration time was observed to be more than 30 minutes for the core was observed percent friability was determined to be 0.029%, indicating durability during coating procedure. Part B: Coating of tablets: The coating procedure was optimized to result in a transparent coat that ascertained uniformity of coat along with compliance with the appearance of the tablets. Optimization of coating parameters play a critical role in obtaining clear transparent coating. Figure 1 demonstrates the comparison between uncoated and coated tablets. Part C: Dissolution profile evaluation: In vitro dissolution of Coated tablets (weight gain: 6% and 9%) with orifice were conducted in USP type 2 apparatus. Figure 2 and Figure 3 mention the results of in vitro dissolution test for weight gain 6% and 9% respectively. A trend of decrease in percent cumulative release was observed in tablets with both 6% and 9% weight gain with decreasing proportion of CA 320S NF/EP in all combination ratios except, with an exception of 25:75 ratio demonstrating the highest percent cumulative release.

Conclusion: Varying the CA 398-10 NF/EP and CA 320S NF/EP coating ratios and its weight gain had a significant effect on the dissolution profiles from osmotic drug delivery system. A trend of decrease in percent cumulative release was observed in tablets with both 6% and 9% weight gain with decreasing proportion of CA 320S NF/EP. Also, with increasing weight gain a decreasing trend of dissolution was observed. Therefore, CA ratios and their weight gain should be considered as critical attributes in the osmotic dosage design.

References: 1. Keraliya RA, Patel C, Patel P, Keraliya V, Soni TG, Patel RC, Patel MM. Osmotic drug delivery system as a part of modified release dosage form. ISRN Pharm. 2012;2012:528079.
2. Vergez et al., Osmotic device containing amantadine and an osmotic salt, Patent No.: US8574626B2

Acknowledgements: The authors would like to acknowledge the funding support provided by Eastman Chemical Company for the study. The authors would also like to thank Eastman Chemical Company for providing the coating materials and Evonik India Pvt. Ltd. and BASF India Ltd., for providing excipient support for this study.

Physical Appearance of Coated Tablets

Dissolution results for tablets with 6% coating weight gain

Dissolution results for tablets with 9% coating weight gain