Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360988
Title: Preparation of novel modified-release dosage forms of diclofenac sodium and ibuprofen
Author: Sujja-Areevath, Jomjai
Awarding Body: Robert Gordon University
Current Institution: Robert Gordon University
Date of Award: 1997
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Abstract:
Mini-matrix multiple unit dosage forms (MUDFs) of diclofenac sodium and S(+) ibuprofen have been prepared. Normal tabletting techniques were used to form the mini-matrices prior to their enclosure in hard gelatin capsules. Four natural hydrophilic gums, namely xanthan, karaya, locust bean and carrageenan gums as well as hydroxypropyl methylcellulose (HPMC) were used as the principle release-retarding agents. Various excipients - lactose, Encompress®, cellulose acetate phthalate (CAP), Veegum F® and Avicel PH101® - were added in different proportions to further modify drug release. The diclofenac sodium mini-matrices (4.5 mm in diameter) were produced by the wet granulation method. The release profiles from several encapsulated minimatrices in phosphate buffer solution (pH 7.0) showed that xanthan, karaya and locust bean gums could sustain the release of diclofenac sodium while the carrageenan gum did not produce a satisfactory sustaining effect. The rank order of decreasing swelling rate in both axial and radial dimensions was xanthan > karaya > locust bean gum and each of these gums showed almost Fickian swelling behaviour. The solvent penetration rates were consistent with the swelling rates. However, the order of decreasing drug release and erosion rates was locust bean> xanthan > karaya gum. For each of these gums, the release behaviour was anomalous indicating that both Fickian drug diffusion and polymer relaxation were involved in the release process. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution period. The study involving xanthan gum showed that the diclofenac sodium release rate declined linearly with a progressive increase in the gumcontent, without changing the release behaviour. However, for high drug: xanthan gum ratio (2:1), the release kinetics changed to Super Case II. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. Mini-matrices containing HPMC produced faster drug release than those containing the three natural gums. There was no synergistic effect between xanthan and locust bean gums on the release of diclofenac sodium from mini-matrices. Variation in the stirring speed (used in the dissolution apparatus) and matrix volume had little effect on drug release, whereas the pH of the dissolution medium greatly affected the release of diclofenac sodium. Following on from the studies involving diclofenac sodium, xanthan and karaya gums were used to produce mini-matrices of S(+) ibuprofen. Excipients with good compressibility characteristics such as lactose, Encompress® and Avicel PH101® were needed in the formulations. At pH 7, higher drug release rates were obtained with karaya gum (Super Case II mechanism) compared with xanthan gum (anomalous behaviour). Solubility differences between the excipients slightly affected the release rate. Compression forces (11 - 26 kN) slightly affected the crushing strength. The minimatrices were relatively stable to variation in temperature (5 - 37°C) and relative humidity (10 - 75%) over a 2 month time period. These studies have shown that near zero-order release of diclofenac sodium and S(+) ibuprofen can be achieved using encapsulated mini-matrices formulations. The release mechanisms and release rates can be adjusted by variation of the type and content of gums and/or excipients.
Supervisor: Cox, Philip J. ; Munday, D. L. Sponsor: Robert Gordon University ; Knoll Pharmaceuticals
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.360988  DOI: Not available
Keywords: Ibuprofen ; Drug release mechanisms ; Mini-matrix multiple unit dosage Pharmacology
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