To enhance the systemic transdermal delivery of papaverine for the treatment of erectile dysfunction, several factors that influence transdermal delivery of papaverine HCl were studied. The effects of membrane types for in vitro permeation study, human skin layers, solvent/cosolvent systems and the penetration enhancers on the transdermal permeation of papaverine HCl were investigated. A combination of caproic acid, ethanol and water in the volume ratio of 50%:30%:20% was chosen as penetration enhancer and incorporated in two gel bases: 18% Pluronic F-127 and 2% Carbopol 940. In vivo skin permeation studies were performed with two loading doses (0.6% and 2%) in rabbits. The flux and permeability coefficient of papaverine HCl through different human skin layers suggested that the major barrier layer for papaverine HCl was residing primarily in the stratum corneum. However, the viable epidermis and dermis layer also contributed certain degrees of diffusion resistance. Differential Scanning Calorimetry study showed that penetration enhancer exhibited a counter effect with papaverine HCl on the temperature and enthalpy in both gels. In vitro drug release study demonstrated significant increases in the steady-state flux, permeability coefficient and enhancement ratio in these gels. Faster drug transports and higher bioavailability were also observed in rabbits. Skin irritation test performed in rabbits demonstrated a mild skin reaction with mean PII scores of 2 and below; however the recovery was fast. In conclusion, caproic acid, ethanol and water in the volume ratio of 50%:30%:20% is an effective penetration enhancer to deliver papaverine HCl transdermally for systemic absorption.

Although the formulation of effective topical drug delivery system is one of the most sophisticated pharmaceutical preparations, it has attracted researchers due to many medical advantages associated with it. Topical drug delivery systems can act superficially on skin surface, locally in dermal layer of the skin or transdermally to provide successful delivery of drug molecules to the systemic circulation avoiding the traditional problems and limitations of conventional routes of drug delivery. Many novel formulations have been utilized topically to enhance either permeability or drug targeting to a specific layer of the skin such as Liposomes, ethosomes, transfersomes, niosomes and catezomes. The main problem with all of these formulations is that there is no distinct barrier between the targeting and localization action to a certain layer of the skin and the transdermal action to the circulation of these preparations. Any minimal change in the formulation could transform it from a local targeting preparation to a systemic one. This article deals with the innovations pertaining to the use of various types of liposomal preparations and liposomal like preparations for topical drug delivery and the patents associated with it.

A method for determining the rate of hydrophilic and hydrophobic drugs release from different types of liposomal dispersions and gels using a dialysis method is described. Dibucaine base and 5-fluorouracil were used as model drugs for a hydrophobic and a hydrophilic drug, respectively. A dialysis technique was employed. Release rates were affected by the rate of rotation of the paddles of the tablet dissolution tester, temperature, and the volume of release medium. The method was used to evaluate the in vitro drug release from hydrophilic and hydrophobic drugs from liposomal dispersions and gels. The in vitro release study of dibucaine base showed no burst effect, while the in vitro release study of 5-fluorouracil showed a clear burst effect with an initial fast release phase followed by a sustained release phase.

The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutaline sulphate tablets (brand A ) relative to a reference product, Bricanyl 2.5 mg tablets (brand 6). The study was a single dose 5 mg randomized crossover one in 15 healthy volunteers in the fasting state. Urine was collected at intervals of 24 h. Total terbutaline excreted in urine as unchanged drug and as conjugates (sulphate and glucuronide) was determined by a developed and validated HPLC method. In-vitro characteristics of both brands were similar. Based on percent of the dose excreted in urine, the oral bioavailability ranged from 33.5% to 75.8% for both brands. Statistics were applied to judge bioequivalence according to USP 24 in-vivo bioequivalence guidance. Results indicated that brand A and B were bioequivalent and hence interchangeable in medical practice.

The present study reports the adsorption of ketoprofen and bumadizone calcium, two non-steroidal anti-inflammatory drugs, on three aluminium-containing antacids. The type of aluminium antacid, the initial drug concentration and the pH of the medium were found to influence drug adsorption. At pH 3–4, binding of both drugs to aluminium hydroxide and dihydroxyaluminium sodium carbonate indicated co-operative adsorption, while adsorption profiles of bumadizone calcium on aluminium glycinate suggested a constant partitioning pattern. pH (1–8) adsorption profiles for ketoprofen and bumadizone calcium binding to aluminium hydroxide and dihydroxyaluminium sodium carbonate passed through a maximum in the pH range 3.5–4.5. Antacid dissolution during the adsorption runs was also investigated at different pH values. The effect of coadministration of ketoprofen and aluminium hydroxide on the bioavailability of ketoprofen was investigated in healthy volunteers. Urine was collected for 24 h following drug administration and samples were analyzed by HPLC for ketoprofen and its conjugates. The urinary excretion data indicated a decrease in drug bioavailability upon coadministration with aluminium hydroxide.

In this paper a hybrid finite element method is applied in evaluation of the stress intensity factors K I and K II of unidirectional fiber reinforced composites. In order to satisfy the stress singularity at the crack tip a singular super-element based on a modified complementary energy principle is developed. The stress and displacement fields in the super-element are expressed in terms of polynomials of two complex variables ξ1 and ξ2 in the transformed ξ-plane. The stiffness matrix of the super-element was determined by using a line integral along the boundary of the super-element. The displacement vector was expressed in terms of the element nodal displacement vector {q} and a properly selected shape function defined along the element boundary.

The in vitro release of ampicillin from 8 brands of ampicillin capsules, using four dissolution apparatus, was determined. These apparatus were the USP dissolution apparatus, the USP paddle stirrer apparatus, the USP disintegration apparatus and the spiral—stirrer apparatus. Significance of the differences in dissolution between brands and between methods were tested. Analysis of variance of the dissolution data showed statistically significant differences between brands and between methods at selected time. The paddle method showed superior discriminating capacity than the other methods. Correlation between the present in vitro data and the previously reported in vivo data, in order to find the apparatus capable to mimic in vivo release of ampicillin from capsules, was also determined.

(1977). Sulphapyridine Crystal Forms. Drug Development and Industrial Pharmacy: Vol. 3, No. 3, pp. 273-290.

The GI absorption of two crystal forms of sulfameter in man was studied. The more energetic crystal form has an absorption rate about 1.4 times as great as that of the water-stable form. Results are discussed in relation to the free energy differences of the two crystal forms (calculated from dissolution rate studies), the viscosity of the medium, and the rate of agitation. The relationship of the results of the present in vivo absorption study to those of in vitro dissolution rate studies is also discussed.