N.H. Choulis

Effects of Excipients on Swelling and Drug Release from Compressed Matrices

AbstractPolymers, and particularly hydrogels, are becoming very popular in formulating controlled-release tablets because they are excellent drug carriers. The effects of hydrophilic and hydrophobic polymers, incorporated in matrices containing soluble (propranolol HCl) or less soluble (flurbiprofen) drugs, on swelling and release kinetics were investigated. The results indicate that swelling and release profiles were affected by the amount of ingredients, the characteristics of the polymer, and the drug substances incorporated in the matrices. Swelling may influence the release rate of the drugs from the matrices. The data obtained from the in vitro dissolution study were evaluated on the basis of a theoretical dissolution equation, by linear transformation of the dissolution curve, and by the Peppas equation. The release mechanisms appeared complex and are affected by the composition of the matrix

Floating and swelling characteristics of various excipients used in controlled release technology

AbstractDuring the past few years, great interest was developed in the subject of floating. In the present study, the floating and swelling characteristics of several excipients used controlled release technology were examined. The floating behavior was evaluated with resultant weight measurements, while a gravimetric method was employed for studying their swelling. The experiments were carried out in two different media, i.e. deionized water and simulated meal in order to monitor possible differences. The results indicated that higher molecular weight polymers and slower rates of polymer hydration are usually followed by enhanced floating behavior. The floating characteristics of all evaluated excipients were improved when simulated meal medium was used. Finally, the combination of resultant weight measurements and swelling experiments can be used to determine in vitro the buoyancy, weight and volume changes of orally administered dosage forms and to predict floating behavior.

Effect of Several Factors on the Mechanical Properties of Pressure- Sensitive Adhesives Used in Transdermal Therapeutic Systems

1bstractThe effects of coating thickness, type of adhesive and type and concentration of enhancer on the mechanical properties of two acrylic pressuresensitive adhesives (PSAs) were investigated using a 2 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° Dynamic Adhesive Strength Peel Test (90° DASPT) and 180° Release Liner Peel Test (180° RLPT). Coating thickness, concentration of enhancer, and type of adhesive did affect the 90° DASPT. For the 180° 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 32 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, α-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 32 was used. The derived equation described the relationship between the 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 griseofulvin gels using Franz diffusion cells

Abstract The strong antidermatophytic action of griseofulvin, following oral administration, results from its concentration in the stratum corneum. However, this route of administration is often associated with various side effects. The purpose of this work was the preparation and in vitro evaluation of several gel formulations of griseofulvin, in which the drug was dissolved, for further clinical studies as an alternative topical dosage form. The in vitro release profiles of these formulations through artificial membranes and excised human skin, determined using Franz diffusion cells, showed that griseofulvin is released from the topical gel formulations employed and diffuses through skin. Additionally, stability studies conducted under room conditions for 16 months indicated that these formulations were adequately stable. Finally, preliminary clinical studies in humans showed that griseofulvin gels were effective and also well tolerated.

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

Abstract 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 nimodipines 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.

Evaluation of maltodextrins as excipients for direct compression tablets and their influence on the rate of dissolution

Abstract The maltodextrins Maltrin M700, M500 and M150 have been evaluated as excipients for direct tablets and their influence on the rate of dissolution was examined. The amount of lubricant appears to play an important role and significantly affects and rate of releasel of drug from the tablet, particularly when the drug is insoluble in water, while the release rate of a soluble drug remains unaffected. All the formulations prepared showed excellent flow and compressibility. Storage of the tablets for 90 days at 45°C was found to have almost no influence on their properties.

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 controlled release matrix using a mixture of hydrophilic and hydrophobic polymers

Abstract A mixture of acrylic resin and carboxymethyl cellulose was used for the preparation of a matrix in an attempt to modify the release rate of propranolol HCl. The dissolution data indicate that it is possible to prepare a dosage form from these polymers capable of delivering the drug at constant rate (zero-order release).

A freeze-dried injectable form of flurbiprofen: 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.