Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337795
Title: Drug release from pellets and matrices based on cellulose ethers
Author: Sadeghi, Fatemeh
ISNI:       0000 0003 5848 9868
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 1996
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Abstract:
This thesis examines the use of hydroxypropylmethylcellulose (HPMC) of different viscosities and ethylcellulose aqueous dispersion (Surelease), alone or in combination with each other, to control the release of metoclopramide hydrochloride or diclofenac sodium from coated pellets or matrices. The glass transitions of the polymeric films were determined by thermomechanical analysis and used as a guideline to select the inlet air temperature in coating operation. The coating procedure was performed using Accela-Cota. Matrices were prepared either by direct compression or wet granulation. Compendial dissolution methodology was used to determine drug release from coated pellets as well as matrices. Release exponents indicating release mechanisms were calculated from the dissolution data. The release of both drugs from coated pellets decreased as the coating load of HPMC increased. However HPMC did not control drug release rate and the majority of both drugs released in less than 1 h. The release exponents for metoclopramide hydrochloride release from HPMC E5 and HPMC E15 coated pellets were -0.45 and -0.46 respectively. The corresponding value for diclofenac sodium was -0.50. These values of n indicate that diffusion is the predominant mechanism for drug release from HPMC coated pellets. The release of both drugs controlled with application of Surelease on drug-layered pellets. Increasing coating load of Surelease extensively decreased the release rates of both drugs and increased the lag times before controlled release was achieved. The release exponent for metoclopramide hydrochloride was independent of coating load and the mean value was -0.60 indicating predominantly diffusion controlled release. However the value of n for diclofenac sodium was higher at low coating loads suggestmg erosion controlled mechanism and decreased as the coating load increased, indicating more diffusion controlled mechanism. The mean value was -0.70. Inclusion of HPMC increased the release rates of both drugs. The Surelease:HPMC ratio had a major role in the release rates of drugs. Addition of HPMC into Surelease did not change the release exponent for metoclopramide hydrochloride (-0.57) from that of Surelease alone and diffusion remained the main mechanism controlling drug release. However the release exponent (-1.28) increased for diclofenac sodium release upon addition of HPMC indicating erosion controlled mechanism. Application of 2% seal-coat of HPMC E5 prior to Surelease resulted in decrease in the release rates of both drugs. However the exponent n and consequently release mechanism remained unchanged for either metoclopramide hydrochloride (-0.60) or diclofenac sodium (-0.69). Generally release of diclofenac sodium from Surelease or Surelease/HPMC coated pellets was faster than metoclopramide hydrochloride. This was attributed mainly to the interaction of the latter drug with the anionic surfactant ammonium oleate present in the Surelease coat. The interaction of metoclopramide hydrochloride with ammonium oleate was confirmed by dialysis studies. Drug release from HPMC matrices was controlled by the polymer content and viscosity. The drug release was also dependent on the solubility of the drugs. Metoclopramide hydrochloride released faster than diclofenac sodium. The release exponent for metoclopramide hydrochloride was in the range of 0.53-0.6.4. The corresponding value for diclofenac sodium was O.59-0.8O. Therefore a combination of diffusion and erosion controlled the release of either drug. The higher value of n for diclofenac sodium may indicate the greater role for erosion than was the case for metoclopramide hydrochloride. The incorporation of Surelease into HPMC K4M matrices considerably decreased the release rate of metoclopramide hydrochloride while that of diclofenac sodium was less affected. The conversion of metoclopramide hydrochloride to its base form was proposed as an explanation. The release exponents for Surelease granulated matrices was -0.56 for both drugs indicating diffusion mainly controlled the mechanism of release.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.337795  DOI: Not available
Keywords: RM Therapeutics. Pharmacology Pharmacology
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