Browsing by Author "LATHA, MS"

Now showing 1 - 4 of 4
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    A NEW METHOD FOR THE SYNTHESIS OF SMOOTH, ROUND, HYDROPHILIC PROTEIN MICROSPHERES USING LOW CONCENTRATIONS OF POLYMERIC DISPERSING AGENTS
    (JOURNAL OF MICROENCAPSULATION, 1995)
    A new method for the synthesis of protein microspheres of wide size range having good spherical geometry and hydrophilicity using very low concentrations of polymeric dispersing agents is reported. The method involves the use of around 1% solution of a biomedical grade aliphatic polyurethane in a mixture of a hexane and dichloromethane as the dispersion medium, as opposed to a 25-30% solution of polymeric dispersing agents employed by previous workers to effect steric stabilization of the protein solution droplets. The versatility of the method is demonstrated by the synthesis of albumin microspheres, as well as those of the amphiphilic protein casein, the latter being more difficult to prepare by surfactant stabilization techniques. Significant advantages of the method include the avoidance of surfactants which become adsorbed on the particles and influence tissue reactions and drug release, and the ease of removal of the polymeric stabilizer from the final product. The method may find application for the preparation of a wide range of protein and polysaccharide microspheres for medical use.
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    BIOAVAILABILITY OF THEOPHYLLINE FROM GLUTARALDEHYDE CROSS-LINKED CASEIN MICROSPHERES IN RABBITS FOLLOWING ORAL-ADMINISTRATION
    (JOURNAL OF CONTROLLED RELEASE, 1995) LATHA, MS; RATHINAM, K; Mohanan, PV; JAYAKRISHNAN, A
    Theophylline loaded bovine casein microspheres were prepared by the glutaraldehyde cross linking of an aqueous alkaline dispersion of the protein containing the drug in a non-aqueous dispersion medium. The cross-linking of the protein droplets was carried out via the organic phase by the addition of varying quantities of glutaraldehyde- saturated toluene. In vitro release of the drug was examined in simulated gastric fluid at 37 degrees C from spheres having three different cross-linking densities. The bioavailability of theophylline released from the microspheres of different cross-linking densities was studied in rabbits following single oral administration. Microspheres with higher cross-linking densities were found to sustain theophylline release even up to 24 h. The peak serum concentrations of such preparations were well within therapeutic limits. Determinations of in vitro/in vivo correlation based on the data showed that a fairly good relationship exists between in vitro and in vivo release. The study demonstrated the potential of cross-linked milk protein as a matrix for sustained release oral preparations.
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    CASEIN AS A CARRIER MATRIX FOR 5-FLUOROURACIL - DRUG-RELEASE FROM MICROSPHERES, DRUG-PROTEIN CONJUGATES AND IN-VIVO DEGRADATION OF MICROSPHERES IN RAT MUSCLE
    (JOURNAL OF PHARMACY AND PHARMACOLOGY, 1994)
    Glutaraldehyde cross-linked casein microspheres were loaded with 5-fluorouracil (5-FU) from concentrated aqueous solutions of the drug after the microspheres were synthesized and cleaned. In-vitro release of the drug was examined in phosphate buffer in the absence and in the presence of protease at 37 degrees C. Drug release data showed that only about 20% of the drug is released in the absence of protease even after 5 days, while digestion of the matrix with protease released the entrapped drug completely in about 24 h. A protein-drug conjugate was synthesized via carbamoyl linkage using 6-(5-FU-1-yl)hexyl isocyanate and the drug release was examined in phosphate buffer at 37 degrees C. Release from the protein-5-FU conjugate was slower compared with the release from microspheres in the presence of protease. Implantation of placebo microspheres of different cross-linking densities in the gluteal muscle of rats showed no adverse tissue reactions over a one-year period. Histopathological examination of the tissues containing injected microspheres suggested that the biological life of casein microspheres in muscle is about 6 months, which is three times that of cross-linked albumin microspheres.
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    GLUTARALDEHYDE CROSS-LINKED BOVINE CASEIN MICROSPHERES AS A MATRIX FOR THE CONTROLLED-RELEASE OF THEOPHYLLINE - IN-VITRO STUDIES
    (JOURNAL OF PHARMACY AND PHARMACOLOGY, 1994)
    A controlled release dosage form of theophylline in the form of microspheres using the milk protein casein as the matrix is described. Glutaraldehyde cross-linking of an aqueous alkaline solution of the protein containing the drug, dispersed in a mixture of dichloromethane/hexane having ca. 1% of an aliphatic polyurethane as the suspension stabilizer, led to the formation of the drug-loaded microspheres. Drug incorporation efficiency of around 80% could be achieved by the technique. Release profiles of the drug were examined in simulated gastric and intestinal fluids at 37 degrees C. It was observed that the release was diffusion-controlled and followed the Higuchi model. Release characteristics were influenced by the cross-linking density, particle size and the extent of loading. Data obtained indicate that the natural milk protein casein could be used as a matrix for sustained release oral dosage forms.