Sadeghi, F (1996) Drug release from pellets and matrices based on cellulose ethers. Doctoral thesis, Liverpool John Moores University.

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Abstract

T.his t~~sis examines the use of hydro~yprol?ylmethylcellulose (HPM~) of di.tJer~nt VIScosities and ethylcellulose aqueous dispersion (Surelease), alone or m 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 m 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 E 15 coated pellets were "0.45 and .. 0.40 respectively. The corresponding value for diclofenac sodium was ..0.50. These values of 11 indicate that diffusion is the predominant mechanism for drug release from HPMC Cl lilted 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 rnetoclopramide hydrochloride was independent of coa.ting load and the mean value was ..0.00 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 ~PMC increased the release rates of both drugs. The Surelease:HPMC ratio had a major role m the release rates of drugs. Addition of HPMC into Surelease did not change the release exponent for metoclopramide hydrochloride (-0.57) from that of Surelea se alone and diffusion remained the main mechanism controlling drug release. However the release .exponent ("1.2X) increased for diclofenac sodium release upon addition of HPM~ Indicating erosion controlled mechanism. Application of 2% seal-coat of HPMC E5 pnor 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 (,,0.00) or diclofenac sodium ( .. 0.09). Generally release of diclofenac sodium from Surelease or SureleaselHPMC 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 metoclupramide hydrochloride was in the ra_nge of 0.53:0.6.4. The ~~)rre.sponding v~ue tor diclofenuc sodium was O.59-0.XO. Therefore a combination of diffusion and erosrnn 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 "0.50 for both drugs indicating diffusion mainly controlled the mechanism of release.

Item Type:	Thesis (Doctoral)
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy & Biomolecular Sciences
Date Deposited:	20 Dec 2016 12:41
Last Modified:	03 Sep 2021 23:28
DOI or ID number:	10.24377/LJMU.t.00005132
URI:	https://researchonline.ljmu.ac.uk/id/eprint/5132

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