In vitro evaluation of nimodipine permeation through human epidermis using response surface methodology.

An optimization technique (response surface method) was used in order to investigate the effect of the combination of two enhancers, namely caprylic acid and cineol on nimodipine's permeation through human cadaver epidermis. Using this quadratic model it was found that at 24 h the increase of the permeation of nimodipine it was mainly due to the effect of caprylic acid. On the contrary, it was shown that at 48 and 72 h the combination of the two enhancers contributed to the increase of the permeation. The greater Q(gel)/Q(control) values, at all time intervals (24, 48 and 72 h), were obtained when the concentration of cineol and caprylic acid range from 3.0 to 5.0% (v/v) and 8.0 to 9.5% (v/v), respectively.

Effect of several factors on the mechanical properties of pressure-sensitive adhesives used in transdermal therapeutic systems.

The effects of coating thickness, type of adhesive, and type and concentration of enhancer on the mechanical properties of two acrylic pressure-sensitive adhesives (PSAs) were investigated using a 2(4) factorial design and an optimization technique. Sixteen formulations containing 0% or 10% of either caprylic acid or methyl laurate in two different PSAs, namely Duro-Tak 87-2196 and Duro-Tak 87-2097, were prepared. The adhesive properties of these laminates were evaluated by applying the 90 degrees Dynamic Adhesive Strength Peel Test (90 degrees DASPT) and 1800 Release Liner Peel Test (180 degrees RLPT). Coating thickness, concentration of enhancer, and type of adhesive did affect the 90 degrees DASPT. For the 180 degrees RLPT, the most significant factors were coating thickness and concentration of enhancer, with a strong interaction observed between the two. Coating thickness and concentration of enhancer were also used to create mathematical models that correlated these factors with the mechanical properties of the PSAs. For this purpose, the optimization technique 3(2) was applied. It was found that the correlation of the above factors can be adequately described with polynomial equations, which can be used for predicting the mechanical properties of the laminates containing the above PSAs and methyl laurate (0%-10%).

Optimization of the pelletization process in a fluid-bed rotor granulator using experimental design.

This study examined the effect of rotor speed, amount of water sprayed, and atomizing air pressure on the geometric mean diameter and geometric standard deviation of pellets produced in a fluid-bed rotor granulator using a 23 factorial design and an optimization technique. Pellets were prepared by wet granulation. Equal amounts of microcrystalline cellulose, alpha-lactose monohydrate, and distilled water were used as the granulation liquid. The size and the size distribution of the pellets were determined by sieve analysis. The size of the pellets was found to be dependent on the amount of water added, while an increase in rotor speed decreased their size. Both factors were found to be statistically significant (P <.05). The effect of atomizing air pressure on pellet size was not statistically significant. None of the 3 factors significantly affected the geometric standard deviation of the pellets. The rotor speed and the amount of water sprayed were further selected in order to construct a mathematical model that correlates these factors with the geometric mean diameter of the pellets. For this purpose, the optimization technique 3(2) was used. The derived equation described the relationship between the selected factors and the size of the pellets. As a result, the experimental design techniques applied were found to be suitable in optimizing the pelletization process carried out in a fluid-bed rotor granulator.

Development and in vitro evaluation of nimodipine transdermal formulations using factorial design.

The in vitro permeation of nimodipine through human cadaver skin, as a preliminary step toward the development of a transdermal therapeutic system, was investigated. In vitro release studies were carried out using modified Franz diffusion cells and human epidermal membrane, taken from full-thickness cadaver skin by heat separation technique. To estimate the effect of the type of enhancer, the concentration of enhancer and the concentration of the gelling agent on the permeation of nimodipine, a 2(3) factorial design was involved. The type of enhancer was further evaluated, because it was found to be important for the permeation of nimodipine; the concentration of enhancer and the concentration of the gelling agent were kept at their optimum levels in all experiments. Six groups of enhancers (alkanols, alkanoic acids, alkanoic acids ethyl esters, caprylic acid alkyl esters, essential oils and some other enhancers) were examined for their ability to increase the permeation of nimodipine. It was found that myristyl alcohol, caprylic acid, L-menthol, and oleic acid gave better permeation rates at 24 hr, with oleic acid being the better enhancer, and higher permeation rates at 48 and 72 hr were achieved only when cineol was used.

A freeze-dried injectable form of ibuprofen: development and optimisation using response surface methodology.

In this study a complex of Ibuprofen and b-Hydroxypropylcyclodextrin was prepared employing a freeze drying method. The production parameters and the final specifications of this product were optimized by using response surface methodology. The results show that the freeze dried complex meets the requirements for solubility to be considered as a possible injectable form.

The effect of modification of acrylic resins on controlled release and bioadhesion.

The effect of various treatments on the properties of an acrylic matrix was studied, in terms of its swelling properties in buffer solution. The release of two types of drugs from those matrices and their bioadhesive character were also considered. Calcium stearate and sodium lauryl sulfate were used as additives for the matrix treatment. 2-Hydroxyethyl methacrylate was also used as a reactive agent for the acrylic resin treatment. The main function of the above chemicals is the modification of the hydrophilic/hydrophobic character of the matrix. This investigation showed that controlled release systems can be designed by adjusting the matrix properties via additives or chemical reaction.

Consistency study of semi-solid pharmaceutical preparations.

The study of the consistency of a number of semi-solid pharmaceutical preparation, namely: simple ointment base, paraffin ointment base, emulsifying ointment base and soft paraffin (m.p. 47--49 degrees C) was conducted using an apparatus designed for the purpose in this laboratory. Factors such as temperature and shearing stress of motive force were taken into consideration. A mathematical equation was developed for the extrapolation of the results.

NMR studies of sustained release methadone tablets.

NMR studies for the identification of methadone in sustained release tablets is conducted. Up-field shifts of the N-methyl and phenyl groups of the compound were observed. These changes indicate an increased lipid solubility and therefore better absorptivity of the drug in the current form.

Long acting methadone formulations.

Studies conducted in this laboratory have indicated the feasibility of producing long-acting methadone tablets. In examining further, methadone hydrochloride suspensions were developed using spermaceti or eudragit retard-1 for particle coating. These procedures involved the addition of the active compound (methandone hydrochloride) to: a) melted spermaceti which was dried, and the dried mixture was pulverized and added to a methyl cellulose water solution; afterwards wild cherry syrup was added to the suspension, and b) Eudragit retard-1 crystals which were pulverized, dissolved in acetone/isopropanol (1:1) solvent system, dried, and to this product again the suspending agent methyl cellulose was added followed by wild cherry syrup to produce suspensions containing 10, 20, and 30 mg/ml methadone. These formulations were further used for in vivo studies, in male albino rats of Wistar strain. The pain threshold method was utilized in order to determine the duration of methadone. Over 75 h resistance to pain was recorded. Using the same technique, suspensions of methadone-naloxone combinations and the salts methadone-alpha-naphthalenesulfonate and methadone-o-benzoylbenzoate were prepared and examine similarly.

Long acting methadone formulation. Part 3: Preparation and in vivo evaluation of tablets containing methadone salts and methadone-naloxone combinations.

The preparation and in vivo evaluation of the methadone salts, methadone-o-benzoylbenzoate and methadone-alpha-naphthalenesulfonate, and a number of methadone-naloxone formulations, in the form of three layered slowly eroding tablets, were examined. Male albino rats of the Wistar strain were used as experimental animals and the results indicated that a prolongation of the resistance to pain threshold was attained, though severe side-effects were observed. A number of animals died during these experimental procedures.

Sustained release methadone salts and methadone-naloxone mixtures. Part 2: In vitro studies of methadone release.

Various tablet formulations, using two methadone salts namely methadone-alpha-naphthalenesulfonate and methadone-o-benzoylbenzoate and a number of methadone-naloxone combinations were prepared. The quantities of methadone released from these tablets in simulated gastric and intestinal fluids were examined using spectrophoto-metric studies. All formulations followed a typical release pattern, indicating a high degree of consistency of the formulations.

Methadone salts. Part 1: preparation and identification.

The preparation of two methadone salts, namely: methadone-alpha-naphthalenesulfonate and methadone-o-benzoyl-benzoate is described. The prepared compounds were confirmed by t.l.c. and IR spectroscopic studies.

Long acting methadone.

Tablets were prepared using pan-coating, congealing, plasticization with organic solvents and direct compression methods. The tablets were evaluated using the official dissolution test, and an analysis of the active ingredient was accomplished by employing gas-liquid chromatography. The formulation and dissolution characteristics of sustained release tablets, employing the matrix concept to regulate drug release, were studied. Particle size distribution of plastic material influenced the release rates from porous inert matrices, and it was found that incomplete drug release occurred from these preparations. Three-layer slowly-eroding sustained release tablets, using a swellable gum (carbomer) were formulated; by adjusting the proportion of the gum quantitative release of the drug was attained. Approximation of linearity for drug release-time relationship was achieved from three-layer slowly-eroding tablets containing different concentrations of drug in the middle and outer layers. Administration of the above tablets, containing 30 mg of methadone, produced analgesia in male albino rats for approximately 60 h, without undesirable effects.

Migration of amphetamine and mandelic and salicylic acids in various pH buffer solutions examined via thin layer electrophoresis.

The degree of migration of optically active, racemic and non-optically active acids and bases on cellulose, silica gel and alumina thin layers is examined in various pH buffer solutions using thin layer electrophoresis. The results indicate different mobilities of the acidic and basic compounds in the various pH buffers of the experiment.