M. Ghimire, P. Patel, Q. Liu, S. Missaghi, S. B. Tiwari, T.P. Farrell and A. R. Rajabi- Siahboomi. Colorcon Ltd

Transcription

1 Effect of Semipermeable Coating Composition and Opadry Top-Coating Systems on Performance of Push-Pull Osmotic Pump Tablets of a Practically Water Insoluble Model Drug M. Ghimire, P. Patel, Q. Liu, S. Missaghi, S. B. Tiwari, T.P. Farrell and A. R. Rajabi- Siahboomi Colorcon Ltd

2 Push-Pull Osmotic Pump What is Push-Pull Osmotic Pump? 1. Pull layer (drug layer) 2 mm Push layer 3. Semipermeable membrane 4. Drug delivery orifice 5. Cosmetic coating 1 2 S.L. Shamblin, In: H. Wen, K, Park, Oral Controlled Release Formulation Design and Drug Deliver: Theory to Practice. 2010; John Wiley & Sons, Inc., dm dt = dv dt x d = A l k π c dm/dt = release rate, dv/dt = water flux, x d = mass fraction of drug, A = membrane area, l = thickness of membrane, k = membrane permeability, π = difference in osmotic pressure, c = concentration of drug in tablet core

3 Push-Pull Osmotic Pump Mechanism of Drug Release PPOP Tablets 2h 4h 8h 2hr 4hr 8hr 12hr 16hr Drug dissolved 2hr 4hr 8hr 12hr 16hr 12h 16h t Advantage Zero-order drug release independent of ph, ionic strength, and physiological factors within GIT

4 Objective The objective of this study : 1. Effect of semipermeable coating composition comprising cellulose acetate (CA ) along with different grades of PEG (PEG 400, PEG 3350 and PEG 8000) on dissolution profiles 2. To evaluate the effect of various Opadry white top film coating systems (YS , 85F18422 and 89F18626) on performance of developed PPOPs at 6% WG on dissolution profiles.

5 Formulation of Pull and Push Layers for PPOP Tablets of Model Drug Y Material (Supplier) Pull (drug) layer %w/w Drug Y 5.6 POLYOX WSR N-80 (The Dow Chemical Company, USA) Mg stearate (MgSt) (Mallinckrodt, USA) Total 100 Material (Supplier) Push layer %w/w POLYOX WSR Coagulant (The Dow Chemical Company, USA) 64.0 Sodium chloride (Mallinckrodt, USA) 35.0 Pigment, red iron oxide (Rockwood Pigments, Italy) 0.5 Mg stearate (MgSt) (Mallinckrodt, USA) 0.5 Total 100 Target weight of bilayer tablets: 330 mg Pull layer : Push layer ratio: ~2:1 w/w

6 Effect of Semipermeable Coating Composition using Various Grades of PEG Release Profiles of Drug Y PPOP Tablets, Coated to 12% WG of Various Semipermeable Membrane Compositions (n=6) Tablets f2 value PEG PEG 3350 Ref. PEG All PPOPs had a lag time of about 2 hours, independent of PEG Mw. Drug release for PEG 400 and 3350 was similar, while using PEG 8000 led to slightly slower drug release. This The information contained in this presentation is proprietary Colorcon, Inc. and may not be used or disseminated inappropriately. could be attributed to the slightly lower aqueous solubility of PEG 8000.

7 Effect of Various Opadry Top-Coating Systems PPOP tablet with top-coat PPOP tablet without top-coat showing bi-layer tablet with semipermeable membrane

8 Effect of Various Opadry Top-Coating Systems Release Profiles of Drug Y PPOP Tablets, Top-coated with Various Opadry Systems to 6% WG (n=6) Tablets f2 value No topcoat Ref. YS F F Application of Opadry top-coat resulted in smooth surfaces and similar drug release profiles compared to PPOP tablets without top-coat at both 3% and 6% WG. Top-coating to 6% WG was more effectively masking the bilayer appearance of the tablets compared to 3% WG and hence is recommended for the Opadry systems evaluated in this study.

9 Additional Poster:

10 Further information: