Controlling the Release of Highly Dosed and Highly Soluble Drugs - Pharmaceutical Technology

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Controlling the Release of Highly Dosed and Highly Soluble Drugs
The authors formulated bupropion hydrochloride tablets with various grades of methacrylic copolymers and analyzed the properties of the resulting dosage forms. This article is part of PharmTech's supplement "Solid Dosage and Excipients 2010."


Pharmaceutical Technology
Issue 34, pp. s14-s18

Materials and methods

Materials. Bupropion hydrochloride was purchased from Divi's Laboratories (Hyderabad, India). The excipients used for matrix granulation included L-cysteine hydrochloride (Merck Group, Darmstadt, Germany), microcrystalline cellulose (Avicel PH 101, FMC Biopolymers, Philadelphia), povidone K 90 (BASF, Ludwigshafen, Germany), talc (Luzenac, Toulouse, France), calcium stearate (Ferro, Cleveland), and glyceryl behenate (Gattefossé, Saint-Priest France). The study involved Eudragit NM 30 D, Eudragit RS PO, and Eudragit FS 30 D (Evonik Röhm).

Method of manufacturing. Granulation was carried out in a GPCG 1.1 granulator (Glatt, Binzen, Germany). The blending was carried out in a double-cone blender (CTC GMP, M/s Wintech, Mumbai), and the lubricated granules were compressed on a 16-station rotary-compression machine equipped with 10.3-mm circular punches with corresponding dies (CPM D3-16, M/s CLIT, Ahmedabad, India).

Bupropion matrix with neutral polymer. Eudragit NM 30 D is the aqueous dispersion of a neutral copolymer composed of ethyl acrylate and methyl methacrylate (3). The authors used it to develop a matrix polymer.

Requisite quantities of bupropion hydrochloride, diluents, and L-cysteine hydrochloride, a stabilizer that maintains acidic pH in the formulation, were weighed and mixed. Eudragit NM 30 D was sprayed at a programmed rate to obtain a mass of suitable consistency that was dried to achieve loss on drying of 1.5–2.0% w/w. The presifted lubricants were weighed and blended with dried granules and compressed. The targeted tablet weight was 400 mg.

Bupropion matrix tablet with anionic polymer. Eudragit FS 30 D is the aqueous dispersion of an anionic copolymer made of methyl-acrylate, methyl methacrylate, and methacrylic acid. It has an acidic pH (3).

Requisite quantities of bupropion hydrochloride, diluents, and L-cysteine hydrochloride were premixed. Eudragit FS 30 D was sprayed on the above blend at a predetermined rate, and the mass was dried to a moisture content of 1.5–2.0% w/w. The presifted lubricants were weighed and blended with dried granules and compressed into a tablet (8).

Bupropion matrix with cationic polymer. Eudragit RS PO is the powder grade of a copolymer of acrylic and methacrylic acid esters and approximately 5% ammonio methacrylate units (3). Requisite quantities of bupropion hydrochloride, diluents, and L-cysteine hydrochloride were weighed and mixed.

Eudragit RS PO was dissolved in a 9:1 ethanol–water mixture and sprayed at specified rate to obtain a mass of suitable consistency. The mass was dried to achieve a moisture content of 1.5–2.0% w/w. The presifted lubricants were weighed and blended with dried granules and compressed.

The in vitro release of bupropion hydrochloride from all tablets was studied in USP Type II (Paddle) device set at 50 rpm in 900 mL of purified water maintained at 37 ± 0.5 °C. Samples were taken periodically for 8 h and analyzed at 298 nm. The same analytical procedure was employed to determine the release in 0.1 N HCl and 40% ethanolic 0.1 N HCl.

The tablets were packed in sealed high-density polyethylene containers and charged on stability as per the International Conference on Harmonization's guidelines. The assay and dissolution were carried out in accordance with the USP monograph for extended-release bupropion hydrochloride tablets (6).


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