Niosomal encapsulation of the tuberculocidal drug rifampicin

Niosomes are vesicles formed by self-assembly of non-ionic surfactants that have potential applications in the delivery of hydrophobic and hydrophilic drugs intracellularly e.g. to macrophages and hence, are expected to increase the potency, safety and to overcome the resistant strains of M. tuberculosis. Rifampicin niosomes were prepared by the chloroform-film method using Span 60 and cholesterol. Stearylamine and dicetylphosphate were added as the positive and negative charge inducing agents, respectively. Characterization of Rifampicin niosomes was carried out using Differential Scanning Calorimetry [DSC] and Electron Microscopy. Computer presentations of DSC thermograms are provided for drug niosomes, drug free niosomes as well as the individual components of the niosomes investigated, using the Shimadzu-50 DS Calorimeter. Electron micrographs reveal the shape of the investigated niosomes. Rifampicin niosomes, thus prepared and characterized, were investigated for the purpose of optimizing the drug encapsulation efficiency, release profiles and expected increased potency and safety. The latter expectancy is explained by the intracellular targeting behavior of the drug niosomes compared to free drug. The results indicate that for rifampicin neutral niosomes, the molar ratio [Span 60: Cholesterol, 4: 2] exhibited better percentage of entrapment viz., 36.55% compared to 26.98% for the molar ratio [Span 60: Cholesterol, 1:1]. For the negatively charged niosomes, the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 1:1:0.1] exhibited better percentage of entrapment viz., 35.08% compared to 30.64% for the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 4:2:1]. For the positively charged niosomes, the molar ratio [Span 60: Cholesterol: Stearylamine, 4:2:1] exhibited nearly similar entrapment viz., 53.83% compared to 52.80% for the molar ratio [Span 60: Cholesterol: Stearylamine, 1:1:0.1]. The release profiles of these rifampicin niosomes were performed at 37°C, as a trial to anticipate the expected behavior of these niosomes under the hydrodynamic stress of in-vivo conditions. The release profile values for the different niosomes investigated showed that neutral niosomes of molar ratio [Span 60: Cholesterol, 1:1] exhibited the least release values compared to molar ratio [Span 60: Cholesterol, 4:2]. For the negatively charged rifampicin niosomes, the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 1:1:0.1] exhibited less release than [Span 60: Cholesterol: Dicetylphosphate, 4:2:1]. Determination of the tuberculocidal activity, of rifampicin niosomes compared to the free drug, in guinea pigs, is under way

Dissolution rate measurements as a predictory tool for assessing comparative bioavailability of generic ampicillin capsules

The dissolution rate of 12 batches of commercial ampicillin capsules manufactured by four leading pharmaceutical companies was determined by both closed and open dissolution systems. The most consistent results were those obtained by the USP method. The beaker as well as flow-through methods showed higher discriminating ability for differentiating the dissolution behavior of different batches of ampicillin capsules of the same brand. On the other hand, the flow- through method provided best discrimination of the dissolution characteristics of different brands. At the same time, the USP rotating basket method did not afford good discriminating ability for different lots belonging to the same brand or for different brands. The bioavailability of these products was assessed in human subjects according to a Latin square design

Solubilization of certain Analgesics by cetomacrogol 1000

Solubilization of certain nonsteroidal anti-inflammatory drugs, viz., phenacetin, ibuprofen and indomethacin by Cetomacrogol 1000 [Cetomacrogol] has been investigated. The values of the ratio of mole drug solubilized per mole micellar Cetomacrogol revealed that the solubilizing power of Cetomacrogol towards ibuprofen is higher than that for phenacetin or indomethacin. One Cetomacrogol micelle solubilizes 38, 17 and 6 molecules of ibuprofen, phenacetin and indomethacin, respectively. Spectrophotometry as well as solubility measurements in different solvents have been used to provide evidence on the environment of the solubilizate molecule in the micelle. On the basis of the results obtained, it was concluded that these drugs are solubilized as follows: Phenacetin and ibuprofen are solubilized in the hydrocarbon core and in the polyoxyethylene region adjacent to the hydrocarbon core. Indomethacin is wholly solubilized in the polyoxyethylene layer adjacent to the hydrocarbon core. The ability of the surfactants to accelerate the dissolution rate of the drug was also investigated. The dissolution profiles of these drugs in Cetomacrogol revealed marked enhancement of dissolution and there is a good correlation between the dissolution efficiency of the three drugs and their solubility in Cetomacrogol at the same temperature

Pilocarpine hydrochloride liposomal ophthalmic drug delivery system

The drug liposomes were prepared from a mixture of L-alpha-dipalmitoyl phosphatidyl choline, cholesterol with or without a charge inducing agent in the molar ratios 7: 4 :1 and 7: 2: 1. These multilamellar vesicles were prepared by the chloroform film method. The amount of pilocarpine hydrochloride entrapped was estimated, spectrophotometrically and is found to range from 4.85 to 13.5% of the initial amount of drug used for the liposome preparation. Results indicated that uncharged liposome of molar ratio 7: 2 exhibits higher pilocarpine hydrochloride entrapment efficiency than that for the molar ratio 7: 4. The positive and negative liposomes entrapped lower percentages, respectively. The ocular bioavailability of pilocarpine hydrochloride liposomes preparation was assessed by measuring the pupil diameter of Albino rabbits using a pupilometer. The change in pupil diameter due to miotic activity of the drug was calculated. The effect of liposomal formulation on the prolongation of the duration of miotic intensity for pilocarpine hydrochloride was assessed by measuring the time course of miotic intensity over a period reaching 120 hours. All the liposome preparations showed prolongation in miotic response than that observed for the control pilocarpine hydrochloride solution and a marketed pilocarpine eye drops