K. Panduranga Rao

Transdermal absorption of nifedipine from microemulsions of lipophilic skin penetration enhancers

Abstract Oil/water microemulsions of six lipophilic skin penetration enhancers (oil of ylang ylang, lavender oil, cinnamon oil, cineole, menthone and menthol) containing ethanol as emulsifying agent were prepared. These systems were used as vehicles for the percutaneous absorption of nifedipine. The effect microemulsions containing 50 and 25% ethanol on the percutaneous absorption of nifedipine were compared with formulations consisting of solutions of penetration enhancers in 100% ethanol. Microemulsions containing 50% ethanol were found to be superior vehicles for the percutaneous absorption of nefedipine. A probable mechanism by which microemulsions enhance the percutaneous absorption of drugs effectively is explained.

Collagen ophthalmic inserts for pilocarpine drug delivery system

Abstract Pepsin-treated telopeptide-poor foetal calf skin collagen has been employed as a carrier for a controlled release of pilocarpine nitrate. Three types of collagen-pilocarpine nitrate drug delivery systems were developed. In vitro release of pilocarpine nitrate from these systems was studied. The release studies indicated that after an initial boost release, pilocarpine was released at a constant rate following zero-order kinetics. The release of the drug can be manipulated based on the type of modification made on the collagen carrier. The release rate of pilocarpine nitrate could be regulated from 5 to 15 days depending on the modification made on the collagen carrier. Collagen film, because of its biological inertness, structural stability and good biocompatibility, proved to be the most promising carrier for opthalmic drug delivery systems.

Collagen-chitosan composite membranes for controlled release of propranolol hydrochloride

Abstract Composite membranes consisting of collagen and chitosan in various proportions were prepared and characterized by Fourier transform infrared spectroscopy and equilibrium swelling studies. The permeability properties of these membranes for propranolol hydrochloride were studied and compared with those of collagen and chitosan membranes. The permeability properties of the composite membranes were found to depend on the concentration of collagen and chitosan in the membranes.

Release of nifedipine through crosslinked chitosan membranes

Abstract The permeability characteristics of a chitosan membrane using the anti-hypertensive drug nifedipine have been investigated. Chitosan membranes were crosslinked with different concentrations of glutaraldehyde and the effect of crosslinking on the permeability characteristics was studied. Permeation studies were carried out in static glass diffusion cells. With increasing degree of crosslinking a definite decrease in the diffusion coefficient, equilibrium swelling, partition coefficient and permeability coefficient was observed. These data supported the involvement of both pore and partition mechanisms in the transport of a hydrophobic drug such as nifedipine through chitosan/crosslinked chitosan membranes. It has been shown that by altering the permeability of chitosan membranes by different degrees of crosslinking the release of bioactive agents could be programmed.

Gelatin microsphere cocktails of different sizes for the controlled release of anticancer drugs

One of the factors which influences the rate of drug release is the particle size of microspheres. In this investigation three individual sets of gelatin microspheres containing 5-fluorouracil (I-GF) in the mean particle size range of 1–5 μm (I-GaF), 5–10 μm (I-GbF) and 10–15 μm (I-GcF) and three individual sets of gelatin microspheres containing methotrexate (I-GM) in the mean particle size ranges of 20–25 μm (I-GxM), 25–30 μm (I-GyM) and 30–35 μm (I-GzM) were prepared and characterised for drug contents. The in vitro release profiles of each individual set was determined in 0.01 M phosphate buffer, pH 7.4, and compared with that from cocktails consisting of a combination of two or three individual sets of microspheres containing 5-fluorouracil (5-Fu) namely, 1−5 + 5−10μm (C-Ga+bF), 1−5+10−15μm (C-Ga+cF), 5−10+10−15μm (C-Gb+cF), 1−5+5−10+10−15μm (C-Ga+b+cF) and cocktails of methotrexate containing microspheres namely, 20−25+25−30μm (C-Gx+yM), 20−25+30−35μm (C-Gx+zM), 25−30+30−35μm (Gy+zM) and 20−25+25−30+30−35μm (C-Gx+y+zM). The results showed that the controlled near zero order release profiles with more desirable features can be obtained by using cocktail of microspheres of various particle size ranges than an individual set consisting of microspheres in the same particle size range, the benefits of which can be applied in cancer chemotherapy.

Preparation of gelatin microspheres of bleomycin

Abstract A new method for preparing hydrophilic, cross-linked, solid gelatin microspheres of 15–28 μm size has been developed. Two main advantages of this method are the addition of the cross-linking agent in an organic medium to the aqueous gelatin medium and the use of concentrated high polymer solutions as the organic phase for polymeric dispersions. Gelatin microspheres containing bleomycin were prepared by this novel method using concentrated solutions of polymethylmethacrylate.

Preparation, characterisation and in vitro stability of hydrophilic gelatin microspheres using a gelatin-methotrexate conjugate

Abstract The anticancer drug methotrexate (MTX) was covalently linked to gelatin using carbodiimide as the coupling agent. The resulting gelatin-methotrexate conjugate (GMC) was separated by gel filtration and characterised by UV and IR spectroscopy. The drug content of the conjugate was 200 μg MTX/mg gelatin. The GMC was used to prepare biodegradable hydrophilic gelatin microspheres (GMCM) of different mean particle sizes (1–5, 5–10 and 15–20 μm). The in vitro release of MTX from GMCM was investigated in simulated gastric and intestinal fluids. GMCM released MTX in a zero-order manner for 7–9 days in gastric medium and for 8–10 days in intestinal medium. The release data also indicated that the rate of release of MTX decreased with increase in particle size of GMCM. Release of MTX was faster in gastric medium when compared to intestinal medium.

Release characteristics of bleomycin mitomycin C and 5-fluorouracil from gelatin microspheres

Abstract Gelatin microspheres containing the anticancer drugs, bleomycin (BLM), mitomycin C (MMC) and 5-fluorouracil (5-FU) were prepared by crosslinking with glutaraldehyde. The in vitro release of the entrapped anticancer drugs from gelatin microspheres was carried out in phosphate buffer, pH 7.4, at 37°C. Optical and scanning electron microscopic studies of gelatin microspheres before and after drug release were also carried out. The in vitro release of BLM, MMC and 5-FU from gelatin microspheres followed a zero-order release pattern except for an initial ‘burst effect’ observed in the case of 5-FU. Microscopic studies clearly indicated that the spherical shape of the spheres changed gradually due to slow disintegration of the sphere and release of the drug by diffusion.

Collagen-chitosan composite membranes controlled transdermal delivery of nifedipine and propranolol hydrochloride

Membrane-permeation-controlled transdermal devices were fabricated for the controlled delivery of nifedipine and propranolol hydrochloride using composite membranes made of natural polymers chitosan and collagen. Devices were fabricated for a single application daily. The drug release profiles from these devices were evaluated in modified Franz glass diffusion cells using rabbit pinna skin. The data showed that the devices effectively controlled the transdermal delivery of both drugs.

Biodegradable microspheres using two different gelatin drug conjugates for the controlled delivery of methotrexate

Abstract The anticancer drug methotrexate (MTX) was covalently linked to gelatin by the azide coupling-grafting method. Two gelatin-MTX conjugates were prepared by coupling (i) MTX azide to gelatin (GMC-I) and gelatin azide to MTX (GMC-II). The resulting conjugates were separated by gel filtration and characterised by UV and IR spectroscopy. The drug content of GMC-I and GMC-II was 205 μg MTX/mg gelatin and 203 μg MTX/mg gelatin respectively. GMC-I and GMC-II were used to prepare biodegradable hydrophilic gelatin microspheres (GMCM-I and GMCM-II) of different mean particle sizes (1–5, 5–10, 15–20 μm). The in vitro release of MTX from GMCM-1 and GMCM-II was investigated in simulated intestinal fluid. GMCM-I released MTX in zero order manner for 9–11 days in intestinal medium and GMCM-II released MTX in a zero order manner for 7–10 days in intestinal medium. The release data also indicated that the rate of release of MTX decreased with increase in particle size of GMCM. Release of MTX was faster in gastric medium when compared to intestinal medium.