| dc.contributor.author | Tirunellai, Krishnan R. | en_US |
| dc.date.accessioned | 2014-10-21T12:37:19Z | |
| dc.date.available | 1992 | |
| dc.date.issued | 1992 | en_US |
| dc.identifier.other | AAINN80187 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55336 | |
| dc.description | Clofazimine (CLF) is a primary antileprotic drug currently used in the triple combination therapy, recommended by World Health Organization. CLF is poorly soluble in water, which is probably the reason for its low and erratic absorption, from currently marketed soft-gelatin capsule (Lamprene$\sp\circler$, Ciba Geigy). The main objective of this study was to improve the aqueous dissolution of CLF using solid-dispersion technique, which in turn, was also expected to enhance its bioavailability. | en_US |
| dc.description | Solid-dispersions (coevaporates) of CLF were prepared using polyvinyl methyl ether/maleic anhydride copolymer (PVM-MA) as the carrier. In vitro tests showed that the coevaporates had enhanced aqueous dissolution characteristics, as compared to the drug alone or its physical admixtures with the copolymer. The release of CLF from the coevaporates was of zero-order and the dissolution increased with the increase in the copolymer concentration. Surface wettability studies supported the findings of the dissolution studies. Accelerated stability studies of the coevaporate during a 12-week incubation period, indicated no apparent degradation of CLF. The coevaporate was also physicochemically compatible with dapsone, which is generally coadministered with CLF in leprosy treatment. | en_US |
| dc.description | A number of instrumentation techniques including scanning electron microscopy, powder x-ray diffractometry, differential scanning calorimetry, infrared (FT) spectroscopy, UV-visible spectroscopy and also equilibrium solubility studies were employed to characterize the nature of interaction between CLF and PVM-MA in the coevaporates. From these studies it was proposed that CLF and PVM-MA formed an internal-amide salt in the coevaporates. When placed in an aqueous medium, the amide bond hydrolysed, resulting in the formation of a complex. CLF in this complex had enhanced aqueous dissolution. | en_US |
| dc.description | In order to quantify CLF from plasma samples, simple and efficient solid-phase extraction and HPLC methods were developed. Comparative bioavailability studies of the test formulation (coevaporate) and reference formulation (Lamprene$\sp\circler$) were performed using the pig as a model. The studies indicated that the coevaporate was over three times more bioavailable, as compared to the reference formulation. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1992. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.subject | Chemistry, Pharmaceutical. | en_US |
| dc.subject | Health Sciences, Medicine and Surgery. | en_US |
| dc.subject | Health Sciences, Pharmacy. | en_US |
| dc.title | Formulation and evaluation of clofazimine coevaporates. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
