Thesis

Pulsed-release drug delivery and development of the time delayed capsule

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Awarding institution
  • University of Strathclyde
Date of award
  • 2002
Thesis identifier
  • T10573
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Abstract
  • The aim of the present study was to optimise a Time-Delayed Capsule (TDC) formulation for use in clinical practice. The TDC consists of a hard gelatin capsule coated with ethyl cellulose, making it water impermeable. An expulsion excipient and drug-containing tablet is situated within the capsule, and the opening is sealed with an erodible tablet (ET) consisting of hydroxypropylmethyl cellulose and lactose. Following ingestion, gastrointestinal fluids cause the ET to erode allowing fluids to enter the capsule and the expulsion excipient swells to expel the drug tablet. The maximum force of compression (Fmax) for coated capsules was determined pre- and post-exposure to a 90% RH and a 'capsule integrity ratio' (CIR) was calculated. Capsules coated with an organic solvent-based technique were found to maintain greater integrity (CIR ≈ 0.38) than an aqueous based coated capsule (CIR = 0.18).ETs manufactured with 15, 24 and 30% HPMC and were found to correspond to lag- times of 1, 3 and 5 hours before drug release. A wet granulation-processing step, to prepare ETs, increased lag-times, particularly with low HPMC concentrations. Microwave dielectric analysis on the wet granulate prior to tableting gave water dipole relaxation times of 2.9, 5.4 and 7.7 x10⁻8 ms for each HPMC concentration respectively. This indicated the extent of HPMC mobility within the granulation allowing spreading leading to extended ET erosion and increased TDC lag-time. Erosion kinetics of ETs was determined as a rapid first order period followed by zero order erosion. The culmination of this work was a clinical study in man, and a good in vitro-in vivo correlation was shown. In conclusion the Time-Delayed Capsule has been developed to allow drug delivery between lag-times of 1 and 5 hours. The TDC can exploit the potential for temporal targeting of wide range of disease states.
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.248923
Date Created
  • 2002
Former identifier
  • 996438693402996

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