(T1230-07-37) Alternative Aqueous Dispersion System for Enteric Coating of Ibuprofen Tablets

Tuesday, October 22, 2024

12:30 PM – 1:30 PM MT

Presenting Author(s)

VP

Vivek Patel, PhD (he/him/his)

Pharmaceutical Scientist, Applied Sciences
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States

Main Author(s)

VP

Vivek Patel, PhD (he/him/his)

Pharmaceutical Scientist, Applied Sciences
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States

Co-Author(s)

HI

Harold Injety, MS (he/him/his)

Senior Scientist
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States
CP

Carmen Popescu, Ph.D.

Global Pharma/Biopharma Technical Developer
Roquette Pharmaceutical Innovation Center
Gwynedd Township, Pennsylvania, United States
ED

Erik Dixon-Anderson, MS

Head of Analytical RD & CTS
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States
SP

Samuel-RK Paulvia, MS

Senior Scientist Applied Sciences & CTS
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States
PF

Peter Freed, Ph.D. (he/him/his)

Global Head of Customer Technical Support
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States
VT

Vinod Tuliani, Ph.D.

VP & Head of Global Pharmaceutical Science
Roquette America Inc.
Lower Gwynedd Township, Pennsylvania, United States

Purpose: Ibuprofen adverse reactions are well known (gastric pain, bleeding, dyspepsia, mucosal ulcers, etc.), impeding long-term treatment. Enteric coating can manage this side effect and enable the delivery of API to the small intestine. In this study, we propose an alternative aqueous dispersion system for enteric coating based on methacrylic acid copolymer type C.

Methods: The formulation blend for 100 mg ibuprofen strength tablet consisted of 50 % ibuprofen (BOC Science), 37.50 % of mannitol (PEARLITOL^®200 GT, Roquette), 11.25 % of microcrystalline cellulose (MICROCEL® 102 SD, Roquette) and 1.20 % of magnesium stearate (Roquette). Ibuprofen, mannitol, and microcrystalline cellulose sieved from sieve no# 40 and blended in TURBULA^® mixer (WAB T2F) at 49 rpm for 5 min. Magnesium stearate sieved from sieve no# 60 and blended with premixed components for 2 min at 49 RPM. The formulation blend mix was compressed using 10.00 mm standard concave punch (Natoli Engineering) using Korsch XL 100 tablet press at 12.6 ± 0.2 kN compression force with a target tablet weight of 400 mg, compression speed 25 RPM with a force feeder speed of 10 RPM. A Labcoat M5 coater (Model LCM5, O’HARA TECHNOLOGIES, Canada) 12-inch pan was loaded with 800 g of ibuprofen tablets (100 mg/400 mg tablet weight) to apply 3 % seal coating followed by weight gain of 4%, 6%, 8%, 10%, 12%, and 14 % enteric coating. Seal coating solution consisted of 10 % solid content of hypromellose 2910 (TYLOPUR® 606, ShinEtsu). Enteric coating solution contained 25 % methacrylic acid copolymer type C (TABSHIELD G, Kofitech). Tablet coating process conditions are listed in table 1. Dissolution of enteric-coated tablets at different weight gain levels was evaluated using USP apparatus 2 at 75 rpm. Dissolution at two-hour time point was performed in 500 mL of 0.1 N HCl solution (pH 1.2), and then tablets were visually inspected and transferred to 500 mL of pH 6.8 potassium phosphate buffer at temperature of 37 ± 0.5°C. Samples were collected at 120 min (pH 1.2 acidic media), followed by 125 min, 135 min, 150 min, and 180 min in pH 6.8 media. Uncoated ibuprofen tablets dissolution was evaluated in pH 1.2 acidic media (as a control). All samples were analyzed using high performance liquid chromatography (HPLC) at 264 nm.

Results: Uncoated ibuprofen tablets at a hardness of1.51 ± 0.07 MPa with average tablet weight of 403.37 ± 7.98 mg gave sufficient strength to proceed to seal and enteric coating. Dissolution profile (Figure 1) of uncoated tablet showed 15.67 % of release in pH 1.2 at the end of 2 h. Tablet enteric coating layer showed cracks and swelling at 4 % weight gain coating at two hours in in pH 1.2 media. Enteric-coated tablets at 6 % weight gain showed release (4.69 %) of drug in 5 min (125 min dissolution time) in pH 6.8 phosphate buffer with no release in acidic media that reduces the need of going to higher weight gain. Tablets coated at 8, 10, 12, and 14% weight gain displayed release of drug at 15 min (135 min dissolution time) in pH 6.8 phosphate buffer, no API release in pH 1.2 media.

Conclusion: Ibuprofen (100 mg/400 mg weight) showed strong mechanical tablet with low weight variation. At pH 1.2, uncoated tablet releases API, while no drug release for enteric-coated tablets starting at 4 % weight gain. Enteric tablet coated at 4 % weight gain was disqualified due to physical appearance. Aqueous dispersion of methacrylic acid copolymer type C (Tabshield G) can be an efficient alternative solution for enteric coating starting at 6 % weight gain leading to time and cost saving.

Figure 1: Dissolution profile of enteric coated Ibuprofen tablets at different percentage of coating (4%, 6%, 8%, 10%, 12%, and 14%) weight gain.

Table 1: Process condition for seal and enteric coating of tablets.