methylcellulose and coumarin

Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery. Extrusion was carried out with a ram extruder. Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water. Extrudates were characterized for their tensile strength, Young's modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO). Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3.3-4.5% w/w dry weight). Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects. For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly. For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release. This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.

Topics: Administration, Oral; Cellulose; Chemistry, Pharmaceutical; Coumarins; Drug Delivery Systems; Elasticity; Hypromellose Derivatives; Lactose; Methylcellulose; Propranolol; Solubility; Stress, Mechanical; Technology, Pharmaceutical; Tensile Strength; Time Factors; Water

Design of a new dosage form manufactured by laminar extrusion for oral administration of drugs. Different mixtures of materials (microcrystalline cellulose [MCC], hydroxypropyl methylcellulose [HPMC], lactose [LAC], dicalcium phosphate [DCP], coumarin [COU], propranolol hydrochloride [PRO], water [W]) were prepared prior to laminar extrusion. Mono, bi and tri layer extrudates were manufactured and evaluated for extrudability, drying, water uptake and swelling ability and in vitro characterization of the drug release. Good quality extrudates were manufactured with higher HPMC molecular weight and fraction in formulation at an extrusion rate of 400 mm/min and slow drying (forced air stream), otherwise surface roughness, thickness in-homogeneity, bending and shark skin were present in the extrudates. Swelling of extrudates was dependent on HPMC fraction and molecular weight (60% up to 90% weight gain for low and high polymer chains, respectively) and the presence of either MCC or DCP. The release of drug was dependent on its solubility (PRO>COU), the fraction of HPMC (low>high fractions), the type of diluent (DCP>MCC) and number of layers (1>2>3 layers). By designing the number and type of layers, dosage forms with well-defined release-kinetics can be tailored. The study has shown the ability of the technology of extrusion to manufacture a controlled release dosage form in a continuous fashion.

Topics: Administration, Oral; Calcium Phosphates; Cellulose; Coumarins; Delayed-Action Preparations; Dosage Forms; Excipients; Hypromellose Derivatives; Lactose; Methylcellulose; Propranolol; Technology, Pharmaceutical; Water