Enhancement of ketoprofen bioavailability by formation of microsponge tablets.

The release of ketoprofen incorporated into modified release ketoprofen microsponge 200 mg tablets and Profenid Retard 200 mg was studied in vitro and in vivo. The formulation containing ketoprofen microsponges yielded good modified release tablets. An in vivo study was designed to evaluate the pharmacokinetic parameters and to compare them with the commercially available ketoprofen retard tablets containing the same amount of the active drug. Commercial ketoprofen retard tablets showed a more rapid absorption rate than modified release tablets and peak levels were reached within almost 3.6 h after administration. However, the new modified release tablets showed a slower absorption rate and peak levels were reached 8 h after administration.

Effects of the permeability characteristics of different polymethacrylates on the pharmaceutical characteristics of verapamil hyhdrochloride-loaded microspheres.

Microspheres containing verapamil hydrochloride (VRP) were prepared with various polymethacrylates, with different permeability characteristics (Eudragit RS 100, Eudragit RL 100, Eudragit L 100 and Eudragit L 100-55) and also with mixtures of these polymers in a 1:1 ratio using the solvent evaporation method. The aim was to investigate the effects of the permeability of the polymers on drug release rates and the characteristics of the microspheres. To achieve these aims, yield, incorporation efficiency, particle size and the distribution of microspheres were determined, and the influence of the inner phase viscosities prepared with different polymer and polymer mixtures on particle size and the distribution of microspheres were evaluated. Surface morphologies of microspheres were observed by scanning electron microscope. Drug release rates from microspheres were determined by the half-change method using a flow-through cell. The results indicate that microspheres with different surface morphologies and statistically different yields and incorporation efficiencies could be prepared and their particle size and distribution xariances resulted from the viscosity of the inner phase. Dissolution profiles showed that the drug release rate could be modified depending on the permeability characteristics of polymethacrylates.

Effect of different dispersing agents on the characteristics of Eudragit microspheres prepared by a solvent evaporation method.

Eudragit RS microspheres containing verapamil HCl for oral use were prepared using three different dispersing agents: aluminium tristearate, magnesium stearate and sucrose stearate, by a solvent evaporation method. The effects of the type and concentration of the dispersing agents and the inner phase polymer concentration on the size and T63.2%, (the time at which 63.2% of the drug is released) of microspheres were determined by multiple linear regression analysis. The morphology of microspheres was characterized by scanning electron microscopy. The surface of microspheres prepared with sucrose stearate was smoother and non-porous and the drug release from these microspheres was the fastest. When aluminium tristearate or magnesium stearate were used as dispersing agents, the particle size of microspheres became smaller. Increasing amounts of these two dispersing agents led to the accumulation of their free particles onto the surfaces of the microspheres. The drug release from the microspheres was slower than that of the microspheres from sucrose stearate depending on their hydrophobic structures. According to the results of the multiple linear regression analysis among the dispersing agents used, aluminium tristearate showed the best correlation between the examined input (dispersing agent and polymer concentrations) and output (T63.2%. and particle size) variables.

Studies on indomethacin inserts prepared by water-soluble polymers. II. The relation between dissolution rate and swelling behaviour.

Inserts containing indomethacin were prepared using water-soluble polymers such as hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose and polyvinyl alcohol by the film casting method. According to the different characteristics of the polymer used, these inserts exhibit different release kinetics and swelling behaviour. In this study, we examined the relation between swelling behaviour of the polymer and the release of the indomethacin from inserts. Thus an electrical device for measuring the thickness of the hydrated inserts was developed. The thickness of the hydrated inserts was measured by this electrical device at selected time intervals for release studies. The results were interpreted from normalised increases in thickness of the hydrated insert. The mechanism of drug release was identified by means of the value of the ratio R/F, calculated according to the equation developed by Peppas. When the ratio R/F of the insert decreased, drug release from the insert became diffusive. As the normalised thickness of the insert increased, the rate of drug release decreased.

The consolidation and compressibility properties of some novel directly compressible filler-binders.

The aim of this study was to investigate the consolidation and compressibility properties and also the dilution potentials of some novel directly compressible filler-binders. For this purpose, Ludipress and Cellastose 80 (one-body compounds), Tablettose 70 and Tablettose 80 (alpha-mono agglomerated lactose) were selected. They were diluted at predetermined percentages with Spherolac 100 which is a coarse sieved hydrous crystalline lactose. The consolidation and compressibility properties of the prepared powder mixtures were determined. The experimental data were evaluated by using a computer programme (Basic 80).

Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and -independent methods.

In this study, the aim was to apply different comparison methods to dissolution profiles of immediate release commercial film-coated tablets of naproxen sodium in order to (1) evaluate each method in terms of easy application and usefulness and (2) identify the advantages and disadvantages of each method. Dissolution testing was conducted using the USP monograph of naproxen sodium. The applied methods for the comparison of in vitro dissolution profiles are ANOVA-based methods, model-dependent methods, and model-independent methods including difference factor, f(1), and similarity factor, f(2). All the methods appear to be applicable and useful in comparing dissolution profiles. The results show that ANOVA-based methods and model-dependent methods are more discriminative than the f-factors. f-Factors seem to be easier to apply and interpret; only one value is obtained to describe the closeness of the two dissolution profiles. However, a last point for dissolution had to be determined, since the values of the f-factors depend on this point. The application and evaluation of model-dependent methods are more complicated; these methods present an acceptable model approach to the true relationship between percent dissolved and time variables, including statistical assumptions which could be checked. Dissolution profiles can be tested for differences in both level and shape by ANOVA-based methods and these methods provide detailed information about dissolution data which can be useful also in formulation development to match release to a reference product.

Modelling of the solvent evaporation method for the preparation of controlled release acrylic microspheres using neural networks.

The purpose of the present study was to model the solvent evaporation procedure for the preparation of acrylic microspheres by using artificial neural networks (ANNs) to obtain an understanding of the selected preparative variables. Three preparative variables, the concentration of the dispersing agent (sucrose stearate), the stirring rate of emulsion system, and the ratio of polymers (Eudragit RS-L) were studied, each at different levels, as input variables. The response (output) variables examined to characterize microspheres and drug release were the size of the microspheres and T63.2%, the time at which 63.2% of drug is released. The results were also analysed by the multiple linear regression (MLR) to provide a comparison with the ANN methodology. Although both ANN and MLR methods were found to be similar in characterizing the process studied, the results showed that an ANN method gave a better prediction than the MLR method. For the size values of the microspheres, the predictability of the ANN model was quite high (R2 = 0.9602) based on the input variables. A relationship between these variables and size values of microspheres was also obtained by the MLR model (R2 = 0.9050). The performances of both models for the release data from microspheres based on the same input variables were at the level of 53%. According to the results, the ANN methodology can provide an alternative to the traditional regression methods, as a flexible and accurate method to study process and formulation factors.

Influence of swelling degree on release of nicardipine hydrochloride from acrylic microspheres prepared by solvent evaporation method.

The purpose of this study was to prepare and evaluate an enteric coated dosage form of nicardipine hydrochloride (NCH)-loaded microspheres for delivery over a 12-hr period. Microspheres containing Eudragit RS and L with different ratios were prepared by solvent evaporation method and the effect of swelling on the release rate and characteristics was investigated. The change in the diameters of microspheres with time in simulated intestinal fluid (pH 7.5) at 37 degrees C has been studied. Drug release was determined using the flow-through cell method, and related to the degree of swelling (Q) of the microspheres. Q values in turn depended on the ratio of Eudragit RS-L used. Release of NCH from microspheres increased with Eudragit L amount, but no controlled-release pattern was observed. Q values > or = 18.88 caused a slow initial release followed by an accelerated release. Microspheres with an Eudragit RS-L ratio of 1:5.7, Q value of 38.71, and drug release rate of 0.155% min-1 exhibited a remarkable delayed time for erosion to begin (120 min). Thus, microspheres prepared from this formulation may provide an effective enteric dosage form, releasing NCH at a predetermined rate.

Preparation of polymeric microspheres by the solvent evaporation method using sucrose stearate as a droplet stabilizer.

Polymeric microspheres containing nicardipine hydrochloride (HCl) as a reference drug were prepared with the acrylic polymers Eudragit RS and L by the solvent evaporation method. Different concentrations of sucrose stearate as a droplet stabilizer were used. Sucrose stearate affected the diffusion rate of the solvent from the preliminary emulsion droplets to the outer phase for the formation of microspheres. Increasing concentrations of sucrose stearate in the formulations caused increasing porosity on the surface of the microspheres. However, a correlation between the concentrations of sucrose stearate and diameters of microspheres could not be assessed. From this point of view, during processing, applied stirring rate was important.

The solid state stability of oral rehydration salts.

The stability of rehydration salts (Electrolyte Powder B.P.C.) used in the treatment of infantile diarrhoea and cholera, was investigated by examining the discolouration of the salts under different conditions. Colourimetric measurements were obtained with a reflectometer. Browning reactions in the electrolyte solutions were followed by absorption at 284 nm and by the thiobarbituric acid reaction at 443 nm. The original white colour of the mixture began to turn yellow during the second week of exposure at 50 +/- 1 degree C under human conditions. Storage at room temperature caused discolouration only after four weeks. Of the three Hunter's values L, a, b the degree of b increased significantly. Discolouration of the mixture was accompanied by spectral changes. The peaks of the spectra shifted uniformly but did not reach 284 nm. The plot of Hunter's L, a, b against time indicated that decomposition of glucose in the powder into early intermediates followed apparent zero order kinetics. Polymerisation of these intermediates after prolonged storage under adverse conditions is a possibility. It is therefore justifiable to conclude that the rehydration salts should be prepared extemporaneously when required unless strict storage conditions are adhered to.