Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS

Abstract

The objective of this research project was to characterize the drug release profiles, physicochemical properties and drug-polymer interaction of melt-extruded granules consisting of chlorpheniramine maleate (CPM) and Eudragit® FS. Melt extrusion was performed using a single screw extruder at a processing temperature of 65-75 °C. The melt extrudate was milled, blended with lactose monohydrate and then filled into hard gelatin capsules. Each capsule contained 300 mg CPM granules. The release of CPM was determined with the United States Pharmacopeia dissolution apparatus II using a three-stage dissolution medium testing in order to simulate the pH conditions of the gastrointestinal tract. Pore structure, thermal properties and surface morphologies of CPM granules were studied using mercury and helium pycnometer, differential scanning calorimeter and scanning electron microscope. Sustained release of CPM over 10 h was achieved. The release of CPM was a function of drug loading and the size of the milled granules. The complexation between CPM and Eudragit® FS as the result of counterion condensation was observed, and the interaction was characterized using membrane dialysis and H(1) NMR techniques. In both 0.1 N HCl and phosphate buffer pH 6.8, CPM was released via a diffusion mechanism and the release rate was controlled by the pore structure of the melt-extruded granules. In phosphate buffer pH 7.4, CPM release was controlled by the low pH micro-environment created by CPM, the pore structure of the granules and the in situ complexation between CPM and Eudragit® FS.

Interaction Studies of Chlorpheniramine Maleate in Mono and Dihydric Alcohols by Density, Viscosity, and HPLC Methods

“…1). It is a weak base having a pKa value of 9.2 [1]. CPM is easily soluble in water and alcohol due to the formation of salt between a carboxylic group of maleic acid and a tertiary amine group of chlorpheniramine by the process of proton transfer.…”

Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine–Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems

“…In comparison with the traditional tableting process, the formulations for HME were simple, without the physical or chemical disturbances associated with the fillers, binders, and lubricants on the APIs. Therefore, HME is also a potential one-step forming technology to produce various sustained-release delivery systems, such as oral granules (3)(4)(5), mini-matrices (6,7), tablets (8), and implants (9). Shan Yi and Jiandong Wang contributed equally to this work.…”

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“…Granulometry plays very significant role in controlling dissolution of certain drugs Particularly in extended release matrix tablets 2 , in present study compaction behavior of one of the ingredient Magnesium oxide light and its particle size distribution for controlling dissolution rate of model drug with constant polymer composition has been studied, release of drug from matrix tablet depends on gelling/erosion/diffusion pattern but compacted ingredients with their defined particle size range also has its major impact on controlling drug release for certain kind of drugs. 3,4 QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.7 (2).601-06…”

“…In the present study model drug selected is Quetiapine fumarate and is a psychotropic agent belonging to a chemical class, the dibenzothiazepine derivatives. The chemical designation is 2-[2-(4-dibenzo [b, f] [1,4] thiazepin-11-yl-1-piperazinyl) ethoxy]-ethanol fumarate (2:1) (salt). It is present intablets as the fumarate salt.…”