The influence of chitosan and sodium alginate and formulation variables on the formation and drug release from pellets prepared by extrusion/spheronisation.
The influence of the incorporation of two oppositely charged hydrophilic natural polymers, chitosan and sodium alginate, alone and in combination, on the ability of formulations containing a model drug (paracetamol) to form spherical pellets by the process of extrusion/spheronisation and the properties of the pellets, has been undertaken. A statistically experimental design was employed to allow the major factors which determined the properties of the pellets, to be identified. A standardised procedure was used to prepare the pellets with a ram producing the extrudate for spheronisation. Statistical analysis of the results indicated that the formulation variables of the type and level of the polymer, the proportion of the model drug, and the proportion of the microcrystalline cellulose influenced (a) the quantity of liquid binder required to produce a good formulation (narrow size range and high value for the shape factor indicating sphericity), (b) the steady-state extrusion force, (c) the pellet perimeter, (d) the apparent pellet density and (e) the porosity of the pellets. The median size of the pellets of the "good formulation" could only be related to the chitosan and sodium alginate content of the formulations. The proportion of the drug, chitosan and sodium alginate content of the formulation significantly influenced the in vitro dissolution of the model drug (paracetamol). The drug release mechanism differed with the formulation variables, although if the pellets remained intact during the dissolution test, diffusion was the controlling mechanism. There was no significant advantage to be gained by using a mixture of the two polymers in terms of retarding drug release.
Chatchawalsaisin
Jittima
J
Department of Pharmaceutics, The School of Pharmacy, University of London, Brunswick Square, London WC1N 1AX, UK.
Podczeck
Fridrun
F
Newton
J Michael
JM
D000082:Acetaminophen / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000464:Alginates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D020723:Glucuronic Acid / Q000737:chemistry*; D006603:Hexuronic Acids / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013997:Time Factors
D000277:Adjuvants, Pharmaceutic; D000464:Alginates; D004304:Dosage Forms; D004337:Drug Carriers; D006603:Hexuronic Acids; D002686:Chitin; D000082:Acetaminophen; D020723:Glucuronic Acid; D048271:Chitosan