287727 Applications of Nanoclays in Controlled Release of API-Polymer Matrix Prepared by Hot-Melt Mixing

Tuesday, October 30, 2012: 12:50 PM
Allegheny III (Westin )
Nonjaros Chomcharn, Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ and Marino Xanthos, Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark

Polymers have been widely used in oral pharmaceutical products to control the release of active pharmaceutical ingredients (APIs) from a dosage. Adding suitable nanoclays to the polymer matrix can enhance the strength of the matrix resulting in further extended release profile of APIs. This work investigates the effect of anionic clays (hydrotalcite, HT) on the bioavailability of a pH-dependent polymer (Eudragit® L100-55) containing anionic APIs (aspirin, Asp). Eudragit® L100-55 is an anionic copolymer based on methacrylic acid and ethyl acrylate and is dissolved at pH 5.5 and above. Triethyl citrate (TEC) was employed as a plasticizer at the ratio of 1:4 (TEC:Eudragit® L100-55) to reduce the processing temperature. The samples were prepared by hot melt mixing using batch mixer (Brabender®) at 50 rpm and 100°C for 5 minutes. After melt mixing, the samples were pressed into thin discs for further characterization.

In the formulation containing Asp and nanoclays HT (Asp/HT), Asp enhanced the collapse of nanoclay aggregates from multilayer structure to platelets dispersed throughout the polymer matrix, resulting in an increase of tortuosity and melt viscosity. XRD confirmed the collapse of HT due to the lower peak at the 2Ɵ angle of 11.2° and 22.4°. Thermogravimetric analysis (TGA) revealed greater stability of the aspirin-TEC/Eudragit® L100-55 matrix containing 10% HT. The release rate of aspirin from aspirin-TEC/Eudragit® L100-55 matrix containing  HT was significantly prolonged presumably as a result of increased viscosity and possible crosslinking in the presence of Asp/HT combinations.

Dissolution study under simulated intestinal fluid (pH 7.4) at 37°C of the formulation containing Asp/HT revealed that approximately 80% and 90% of aspirin was released over the period of 12 hours and 24 hours respectively whereas an identical formulation without HT released nearly 100% of aspirin within 4 hours. Delayed-release dissolution showed that less than 10% of Asp was released in acid stage (2 hours) in both formulations containing only Asp and Asp/HT. After the pH was adjusted to pH 7.4 (buffer stage), all formulations have similar dissolution profiles as shown under the condition of pH 7.4 medium without exposed to acid stage.

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