1569_poster_mem-pd 131.fh10

Development of a Gastric-Resistant Formulation of Omeprazole with Kollicoat MAE 30 DP and 100 P
and Characterization by USP-Resistance-Test and ESR-Spectroscopy
K. Mäder, Martin-Luther-University, 06099 Halle, Germany K. Bräunig, K. Kolter and K. Meyer, BASF-Aktiengesellschaft, Development Pharma Ingredients, 67056 Ludwigshafen, Germany Coating formulation
Dissolution test of omeprazole in pH change
Dissolution test of omeprazole in pH change
Omeprazole as an acid-labile substance must be administered in a gastric- Film-coated tablets without Na
Film-coated tablets with 10 % Na
resistant formulation. Therefore, enteric coating materials such as methacrylic Formulation I
Formulation II
2HPO4 and subcoating
2HPO4-addition
acid-ethyl acrylate-copolymers like Kollicoat® MAE 30 DP and Kollicoat® Proportion [%]
Proportion [%]
Resistance Test
Dissolution Test
Resistance Test
Dissolution Test
Polymer suspension
The objective of this study was to test the performance of these polymers Kollicoat MAE 30 DP, 6.8 mg/cm², without subcoating Kollicoat MAE 30 DP, 5.8 mg/cm², with subcoating in different thicknesses, the influence of subcoating with Kollicoat® IR on Kollicoat MAE 100 P, 6.6 mg/cm², without subcoating this performance, and also the effect of a 10 % Na Kollicoat MAE 100 P, 5.5 mg/cm², with subcoating tablet core as buffering agent to prevent acid attack.
Pigment suspension
Materials
Tablet cores (table 1), polyvinyl alcohol-polyethylene glycol graft copolymer ® IR, BASF Aktiengesellschaft), methacrylic acid-ethyl acrylate- copolymers (Kollicoat® MAE 30 DP and 100 P, BASF Aktiengesellschaft), 10 20 30 40 50 60 70 80 90 100 110 120 10 20 30 40 50 60 70 80 90 10 20 30 40 50 60 70 80 90 100 110 120 10 20 30 40 50 60 70 80 90 triethyl citrate (Merck KGaA), talc (Riedel-de Haen), titanium dioxide (E171, Kronos), red iron oxide (Sicovit® Red 30, E172, BASF Aktiengesellschaft), Process parameters
disodium hydrogen phosphate dihydrate (Merck KGaA).
Tablet preparation
The dissolved ESR-probe was granulated on Ludipress® in the Diosna ESR-Spectra after 2 h in 0.08 N HCl
ESR-Spectra after 2 h in 0.08 N HCl
mixer V 50 for 5 min at stage 1, sieved using an 800 µm-sieve and dried Film-coated tablets with and without Na2HPO4
Film-coated tablets with and without Na2HPO4
for 20 min at 35 °C in the fluid bed (Glatt GPC 1). All tablet ingredients were blended in the Diosna mixer V 50 for 3 min and compressed on a Polymer: Kollicoat MAE 30 DP
Polymer: Kollicoat MAE 100 P
Kilian RL 15 rotary press at 10 kN compression force.
Tablet formulations
Omeprazole
Omeprazole tablets
ESR-Spectroscopy
with Na2HPO4
ESR spectra were obtained using a 1 GHz Magnetech ESR spectrometer were treated in 0.1N HCl at 37 °C for 1 h and 2 h, removed and investigated.
The coupling constant of the ESR-probe depends on the pH value2).
The distance between the first and the third line of the intergrated ESR spectra was used to determine the coupling constants and the pH No omeprazole was liberated within 2 h in 0.08 N HCl from tablets without Na2HPO4 coated with at least 6 mg/cm² enteric polymer Spectrum
Tablet Coating
Conclusions
A 15 % aqueous solution of Kollicoat® IR was used for subcoating to achieve Tablets with Na2HPO4 and coated with Kollicoat® MAE 30 DP resp. 100 P released up to 7 % resp. 10 % omeprazole. A subcoating of 1 mg/cm² • Kollicoat MAE 30 DP and 100 P are suitable as gastric-
reduced the release to 5 % (Figure 2). All formulations with 10 mg/cm² were resistant coatings at ³ 6 mg/cm².
A standard coating formulation1) was prepared for gastric-resistant coating (Kollicoat® MAE 30 DP, 100 P and pigments).
totally resistant in HCl. After buffering the solution to pH 6.8, all coated tablets liberated > 85 % within 60 min.
• An addition of 10 % Na
The coating was performed in an Accela Cota 24" (Manesty) equipped with 2HPO4 to the tablet core improves the
stability of omeprazole by buffering the penetrating protons but
a Schlick 930/7-1-S35 spray gun in 5-kg batches.
By means of ESR-spectroscopy2) the protons which penetrated the weakens the enteric properties.
tablet core could be detected. The peak intensity of the spectra increases USP-Resistance Test
with the mobility of the ESR-probe, which corresponds to a higher water • The ESR-spectroscopy can successfully be used for acid detection
permeability of the film. In 0.1 N HCl treated tablets containing Na The tablets were tested in a USP-dissolution tester apparatus 2 at 100 rpm in cores of aged or acid treated samples.
spectra showed remarkable additional signals, in opposition to dry and using 0.08 N HCl and phosphate buffer pH 6.8. The liberated omeprazole unbuffered treated cores. The water permeability of tablets with Na was determined by means of UV-VIS (306 nm). The concentration of increases due to a higher pH in the tablet core, which weakens the enteric omeprazole was calculated according to a previously determined coating (Figures 3 and 4). In all measured samples, tablets with Kollicoat® MAE 30 DP-coating were more resistant.
References
1) Generic Drug Formulations with Kollicoat MAE grades, BASF Aktiengesellschaft, July 1999 The pH in the tablet core after 2 h was determined to be < 4.5 without 2) A. Brunner, K. Mäder, A. Göpferich: pH and Osmotic Pressure Inside Biogradable Microspheres During Erosion; Pharm. Research 16, (6), 847-853, (1999)

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