Purpose: Diclofenac sodium (DS) is a non-steroidal anti-inflammatory drug and widely used in various inflammatory conditions1. Immediate-release tablets of DS produce unwanted adverse events in stomach region of the GIT. These adverse events can be avoided/minimized by ensuring drug release in intestinal region of the GIT by coating tablets with pH-dependent polymer(s). The objective of the present studies were to explore feasibility of using Eastman cellulose acetate (CA 320S and CA 398-10) and cellulose butyrate (CAB 171-15) as delayed release coating polymer alone as well as in combination with cellulose acetate phthalate (C-A-P), hydroxypropyl methyl cellulose succinate (HPMCP 55) or Eudragit® L100.
Methods: Core tablets composed of lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose (MW 100k), croscarmellose and magnesium stearate tablets were prepared by wet-granulation method. The coating solution formulations contained polymer(s) and polyethylene glycol 400 in acetone-water mixture. The core tablets were coated with coating polymer(s) at two levels (approximately 5% and 10% w/w). Core tablets and coated tablets were characterized for various quality parameters such as hardness, friability, disintegration and dissolution. The two-step dissolution was performed in 0.1 N HCl and 0.2M phosphate buffer for coated tablets.
Results: The drug did not release from the formulations coated at 5% and 10% w/w at acidic pH. Dissolution was low in formulations coated with cellulose acetate (CA 320S and CA 398-10) or cellulose butyrate (CAB 171-15) when compared with cellulose acetate phthalate (C-A-P), hydroxypropyl methylcellulose phthalate (HPMCP 55) or Eudragit® L100 coated ones. However, combining the cellulosic polymer with other enteric polymer (CAP, HPMCP 55 or Eudragit® L100) increased the dissolution. Dissolution also decreased as coating level increased. The dissolution varied from 16.18 to 98.03% and 6.82 to 94.77% at 5% and 10% coating level, respectively. The dissolution was highest and lowest in tablets coated with coating formulations based on Eudragit® L100 and cellulosic polymer, and HPMCP 55 and cellulosic polymer, respectively.
Conclusion: In summary, Eastman cellulosic polymers (CA 320S, CA 398-10 and CAB 171-15) provide alternate to C-A-P, HPMCP 55 and Eudragit® L100 for delayed release coating with some added advantage in terms of low level of coating is required to achieve similar delayed release/dissolution profile. Cellulosic polymers can also be used in extended release of the drug at intestinal pH and colonic delivery of the drug.
Hamideh Afrooz– Research Assistant, Texas A&M University, Texas
Raktima Bhattacharya– Post Doctoral Research Associate, Texas A&M University, Texas
Phillip M. Cook– Eastman Chemical Company
Ziyaur Rahman– Associate Professor, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas