Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310157
Title: Design and study of a drug delivery system comprising compacted polymer-coated pellets
Author: Dyer, Ann Margaret
Awarding Body: De Montfort University
Current Institution: De Montfort University
Date of Award: 1992
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Abstract:
Due to the physical limitations associated with the size of a hard gelatin capsule shell it has not been feasible in practice to present a low potency drug in the form of a sustained release multiparticulate delivery system. The aim of this work was to design a tablet which, on oral administration, rapidly releases intact polymer coated pellets in which the integrity of the cores and the release retarding membrane is preserved. A comprehensive study is made of the effect of uncoated pellet formulation and pelletization processing variables on the physical, skeletal and tensile properties of uncoated pellets. Investigation into the effect of the drying technique on the properties of uncoated pellets is also reported. This work has shown that the aqueous solubility of pellet components and the drying technique used has a marked effect on pellet diametral strength, elasticity, surface characteristics and in-vitro drug release. Pellets were coated using aqueous dispersions of polymethacrylate, ethylcellulose and silicone elastomer polymers. The effect of the film composition on tensile properties was studied by evaluating the mechanical properties of free-films using the technique of indentation hardness testing. The quality of the film coating and the effect of polymer loading was evaluated using in-vitro dissolution testing and by scanning electron microscopy. It was found that those polymeric film formulations whose tensile properties most resembled the tensile properties of the pellet cores resulted in films which were best able to withstand the applied stress associated with pellet compaction. Those films exhibiting significantly greater elasticity than the uncoated cores resulted in pellets which exhibited a tendency for instantaneous elastic recovery on removal of the applied load; tablet formation was therefore prohibited. Polymer coated pellets were successfully compacted into tablets with an inert direct compression blend comprising large particle size grades of lactose and microcrystalline cellulose. Pellet distribution within the tablet matrix (evaluated by image analysis of tablet sections, microphotography and uniformity of content data) failed to show evidence of particle segregation. Comparative in-vitro release profiles of compacted and non-compacted pellets shows that some physical damage is being caused to pellets as a result of the compaction process. Pellets are rapidly released from the matrix on disintegration of the tablet. Visual observation of released pellets indicated that they were intact, however microscopic examination revealed evidence of impaired surface quality. Pellet damage during compaction appears to be independent of the magnitude of the applied load and fracture of the polymer coating is restricted to those pellets in contact with the surfaces of the punches and die during tableting.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.310157  DOI: Not available
Keywords: 615.1 ; Pharmacology Pharmacology
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