(M0930-12-79) Effect of Different Neutralizers and Their Concentration on Enteric Coating of Hypromellose Phthalate (HPMCP HP-50) and Drug Release in Various pH

Purpose: To study the effect of different neutralizers, their concentration on HPMCP HP-50 enteric coated tablets without compromising the enteric property and check the drug release throughout the GI tract. The study can also be helpful to develop site specific drug release at a particular pH in the GI tract.

Methods: The main objective of this study was to evaluate neutralization effect on the enteric polymer Hypromellose Phthalate (HPMCP HP-50) and check the fluid uptake and drug release in various pH mediums. In this development, Esomeprazole 40mg tablets are prepared and used for evaluation. Tablet weight is 203 mg with 8mm diameter and 80N tablet hardness. The Esomeprazole tablets are seal coated with aqueous solution of Pharmacoat^® 606 for 3% weight gain. In seal coating layer along with Pharmacoat^® 606, triethyl citrate is used as a plasticizer (5% to polymer) and talc is used as an anti-tacking agent (10% to polymer weight). Seal coated tablets are further coated with enteric coating polymer HPMCP HP-50 for 10% weight gain. These tablets are considered standard for evaluation against neutralized enteric coating tablets to measure fluid uptake and drug dissolution. Neutralized enteric coating is done 10% polymer weight gain for comparison against standard. For neutralization, follow the below procedure, a. Disperse HP-50 in water under constant stirring. pH of the dispersion will be between 2.9 - 3.1. b. Prepare alkalizer solution and add to step "a" and continue stirring. pH will be 4.5 - 4.7. c. Add isopropyl alcohol (IPA) and continue stirring till solution becomes clear. pH of the solution will be 5.2 - 5.3. The amount of alkalizer to be added in step "b" is calculated as per given below formulae. 1. Sodium hydroxide (NaOH) as a neutralizer. Amount of NaOH (g) per 100g of HPMCP . = [percent neutralization x Phthalyl content (%) x 40] / [100 x 149]. 2. Ammonia (NH₃) as a neutralizer. Amount of NH₃ (g) per 100g of HPMCP. = [percent neutralization x Phthalyl content (%) x 17] / [100 x 149]. 3. Sodium bicarbonate (NaHCO₃) as a neutralizer. Amount of NaHCO₃ (g) per 100g of HPMCP. = [percent neutralization x Phthalyl content (%) x 84] / [100 x 149].

Results: Enteric coated tablets by neutralisation were subjected to fluid uptake test and drug release was measured at each pH level (1.2, 4, 4.4). Fluid uptake results in different pH medium is tabulated in Table no. 01. Acid protection in pH 1.2 and drug release in pH 6.8 is shown in Fig. 01 and drug release throughout GI tract is shown in Fig. 02 keeping same concentration of neutraliser.

Conclusion: As the neutralization level increases the coating membrane become more permeable. Hence, there is increase in fluid uptake. 20% ammonia neutralization trial complies fluid uptake limits (NMT 5%). Sodium hydroxide effectively neutralized the HPMCP HP-50 resulting in increase in permeability of coating membrane as compared to ammonia and sodium bicarbonate. Sodium hydroxide neutralization gives drug release at lower pH 4.4 whereas sodium bicarbonate and ammonia neutralization give drug release at pH 5.0 even though they are coated at the same percentage (10%). The site-specific drug release can be achieved between pH 1.2 and pH 5.0 by selecting suitable alkalizer and by adjusting the percentage neutralization of alkalizer during HPMCP coating.

Table no. 01 Fluid uptake in different pH medium with varying concentration of neutralizers

Fig no. 01 Drug release from neutralized HP-50 enteric coating layer at pH 1.2 and pH 6.8

Fig. No. 02 Drug release from Esomeprazole enteric coated tablets throughout GI tract after 20% neutralization