Adhesion testing of polyurethane matrix patches for transdermal delivery of testosterone.

The 180 degrees peel test was applied to measure adhesion of three experimental polyurethane (PU) matrix patches and one commercial patch, Testopatch, on human volunteers skin. Comparing the results with those measurements on stainless steel or leather, a significant correlation between the leather data and the skin measurements was found. In contrary to results from stainless steel tests, all of the PU patches achieved better adhesion on skin than the commercial patch.

Polyurethanes as self adhesive matrix for the transdermal drug delivery of testosterone.

The new technology to manufacture transdermal active patches without solvents or increased temperatures described here is based on polyol and isocyanate reacting to polyurethane (PU) in the presence of the drug. The technology was proven using testosterone (T) as the drug and N,N-Diethyl-m-toluamide (DEET) and Limonene (L) as enhancers for skin permeation. The experimental patches varied in drug content and enhancer concentration. The patches were evaluated regarding adhesion to stainless steel or leather, in vitro drug release and T permeation across human cadaver skin using Franz cell. Comparing the results with those of a parallel investigation of the commercial product, Testopatch(®), adhesion to leather and in vitro drug release of the experimental patches were found to be higher. The steady-state flux (J(SS)) of T from the experimental patches was found lower than Testopatch(®). The flux of the experimental patch P3, which had the highest concentration of DEET and a low concentration of L was comparable to J(SS) of the commercial product, Testopatch(®).

Optimization of a metformin effervescent floating tablet containing hydroxypropylmethylcellulose and stearic acid.

This study optimizes the composition of an effervescent floating tablet (EFT) containing metformin hydrochloride (M) regarding tablet hardness (H), time to dissolve 60% of the embedded drug (t60%), and buoyancy, the floating lag time (FLT). A simplex lattice experimental design has been used comprising different levels of hydroxypropylmethylcellulose (HPMC), stearic acid (SA), sodium bicarbonate (SB) as tablet matrix components, and hardness (H), t60%, FLT as response variables. Two models have been applied to decide which composition will result in Fickian diffusion or in overlapping of two dissolution mechanisms, diffusion and matrix erosion. Three of EFT showed the two dissolution mechanisms but most of EFT showed Fickian diffusion only. Checking the experimental response by a linear, quadratic, special cubic and cubic model using multivariate regression analysis resulted in best fit for the cubic model. Overlaying the results for the cubic model under constraints defined shows the domain of accepted values of response variables. The optimized EFT shall have been included HPMC between 15.6% and 24.2%, SA between 12.8 and 15.6% and SB between 16.1% and 17.5%. The result of this study has been critically evaluated considering analogous EFT described in literature.

Adhesive backing foil interactions affecting the elasticity, adhesion strength of laminates, and how to interpret these properties of branded transdermal patches.

Standard tensile strength and peel adhesion tests were carried out to investigate interactions of pressure-sensitive adhesives (PSAs) with several backing foils used for transdermal patches. Seven branded transdermal patches (Alora, Cutanum, Estraderm MX 50, Estraderm TTS 50, Fem7 -50 micrograms, Menorest, Oesclim) were included in the investigation. Their skin adhesion measured in several clinical trials was compared with the results of the laboratory measurements according to PSTC-1 (Peel Adhesion for Single Coated Tapes 180 degrees Angle, Pressure Sensitive Tape Council, Illinois, 1996), such as Young's modulus at 3% elongation and peel adhesion to stainless steel. Data obtained for the PSA-coated backings (laminates) show increasing elasticity with increasing PSA thickness. Interactions of PSAs with backing foil became evident in significant changes in Young's modulus by low PSA thickness, as seen for the silicone adhesive. The Young's moduli of the laminates were found to be influenced not only by the elasticity of the backing foil but also by the chemical structure of the PSA. There was no correlation between the elasticity and peel adhesion of both the laminates and the branded patches. Likewise, for the branded patches the peel adhesion to stainless steel does not correlate with skin adhesion values obtained from clinical trials. The Young's modulus of the branded patches was between 4 N/mm2 (Oesclim) and 501 N/mm2 (Fem7). For the branded transdermal patches no correlation was found between Young's modulus and both the peel force on stainless steel and the skin adhesion reported in studies.

X-ray diffraction, differential scanning calorimetry and thermogravimetry combined with infrared analysis of freeze-dried prednisolone hemisuccinate.

In this study, the thermal behaviour of freeze-dried prednisolone hemisuccinate (Prednisolut) was investigated by means of X-ray scattering, differential scanning calorimetry (DSC) and fourier transformation infra-red analysis (FT-IR).

A melatonin preparation with a pulsatile liberation pattern: a new form of melatonin in replacement therapy.

Using melatonin (MLT) as a circadian synchroniser in humans to treat rhythm disorders, it is desirable to have controlled-release dosage forms. Following in vitro liberation tests, one fast-release form containing 5 mg MLT (capsule A) and two oral pulsatile-dosage forms containing 10 mg MLT each (capsules B and C) were studied in a randomised, single-dose, threefold cross-over study in 15 healthy male volunteers after investigation of capsule B in dogs. Mean peak concentrations of MLT in serum (pmol/ml) were reached between 0.5 h and 0.75 h: Cmax1 20.7 (A), 16.4 (B), 9.7 (C). Capsules B and C released a second MLT pulse after about 3.5 h with Cmax2 of 13.0 and 17.5 pmol/ml, respectively. The time course of the renally excreted main metabolite 6-sulphatoxymelatonin (aMT6s) correlates with that of changes in MLT serum concentrations. The kinetic profile of the delivery system is adjusted to the pattern of sleep maintenance disturbances.

Evaluation of an oral pulsatile delivery system for melatonin in humans.

Using melatonin (MT) as a circadian synchroniser in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver MT in accordance with its endogenous secretory pattern as well as preparations that release MT in a pulsatile way. In this paper we describe two oral pulsatile dosage forms containing 10 mg MT each (capsules B and C) and a fast-release form containing 5 mg MT (capsule A) studied in a randomised single-dose, threefold cross-over study in 15 healthy male volunteers. The concentrations of both MT in serum and its main metabolite 6-sulfatoxymelatonin (aMT6s) in urine were analysed by means of specific radioimmunoassays up to 10 h p.a. of the MT preparations. Mean peak concentrations of MT in serum were reached between 0.5 h and 0.75 h (Cmax[1] pmol/ml): 20.7 (A), 16.4 (B), 9.7 (C). The capsules B and C released a second MT pulse after about 3.5 h with Cmax[2] of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality for the MT preparations studied was calculated by determining the AUC0-infinity (pmol/ml.h): 18.4 (A), 36.1 (B), 42.4 (C). The terminal serum half-lives of MT ranged between 0.64 and 0.84 h. The time course of the renally excreted aMT6s correlated with that of changes in MT serum concentrations.

[The effect of bioadhesiveness of viscous solutions with naphazoline hydrochloride on the elimination of the drug from the eye of swine]. / Einfluss der Bioadhäsivität von Schleimen auf die Elimination von Naphazolinhydrochlorid vom Auge des Hausschweines.

Solutions of sodium carboxymethylamylopectine, tragant, hydroxyethylcellulose, polyvinylalcohol, polyacrylic ester D 339, polyacrylic ester D 340 and polyacrylic acid, all of the same viscosity and with the same concentration of naphazoline hydrochloride, were applied on the isolated eye of pig. After sink the eye in a solution of sodium chloride the elimination of the drug from the eye was investigated. The results were compared with the bioadhesion of the viscous solutions measured ex vivo on the intestine of pigs. There were correlations between the eliminated mass after 5 min, after 30 min and the bioadhesion. Furthermore the calculated initial elimination constant was indirect proportional to the bioadhesion. The elimination of the drug between 5 and 30 min was independent on the bioadhesion.

[The effect of mucous excipient concentration on bioadhesion ex vivo]. / Einfluss der Schleimstoffkonzentration auf die Bioadhäsion ex vivo.

The bioadhesion of aqueous solutions of polyacrylics (1-3), hydroxyethylcellulose (4), sodium carboxymethylamylopectin (5), polyvinylalcohol (6) and tragant (7) was investigated using a tensiometer and fresh intestine of pigs. It was dependent on the concentration of the excipient as described by a quadratic equation and found in the maximum from 244 Pa (7) to 554 Pa (4). The maximum of bioadhesion corresponds to the concentration of the excipient from 0.15% (2) to 23.7% (4) and to the viscosity of the solutions from 0.11 Pa.s (3) to 3.6.10(6) Pa.s (4). There was not a correlation between the viscosity and the bioadhesion.