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Purpose: To evaluate the impact of lesion size on the observed growth of the choroidal neovascularisation (CNV) following the first application of photodynamic therapy (PDT)., Methods: A retrospective study of consecutive patients with subfoveal classic CNV or predominantly classic CNV undergoing first verteporfin photodynamic therapy (VPDT) according to treatment of age-related macular degeneration with photodynamic therapy (TAP) protocol between June 2005 and September 2005. Patients were classified into two groups according to baseline greatest linear dimension (GLD) at the time of VPDT monotherapy. Group 1 comprised patients with lesion GLD less then 2000 microm and Group 2, patients with lesion GLD 2000 microm or larger. Difference between the mean GLD at baseline and at three months post-treatment were investigated for clinical significance using the paired t-test., Results: Group 1 (n = 16) showed a mean change in GLD from 1380.25 microm to 2031.25 microm, while Group 2 (n = 26) showed a mean change of 2909.26 microm to 3023.07 microm. Data of mean percentage change in GLD for Group 1 showed a 51.97 per cent increase in the lesion size [95% CI, 22.93 - 81.01%] in comparison to Group 2, which showed only 5.8 per cent increase in the lesion [95% CI, -9.65 - 21.61%]. Comparison of the mean percentage change in GLD between the two groups showed a statistically significant difference (p = 0.003)., Conclusions: Our study demonstrates that following the first application of VPDT, smaller lesions enlarge disproportionately more than larger lesions. As we have entered into the era of using angiostatic agents in combination with VPDT, it may be important to evaluate this effect with regards to the timing of VPDT commencement.

Introduction: Khat (Catha edulis) is an evergreen tree/shrub that is thought to affect sexual motivation or libido. Its positive effect on sexual desire is more frequently observed in females than in males and occurs when khat is chewed. Thus, khat's effects on sexual behavior may depend on the release mode of its active constituent., Aim: This study aimed to investigate the effect of dried khat alkaloids on the sexual motivation and estradiol levels of female rats, with special emphasis on the importance of the sustained release effect., Methods: Dried khat leaves were extracted and isolated. The alkaloids in khat extract were identified and calculated using thin layer chromatography and high-performance liquid chromatography. The isolated khat extract was microencapsulated using a phase separation coacervation method. The morphology, particle size, yield, drug loading, and entrapment efficiency were evaluated. The in vitro release and stability of alkaloids in khat extract and in khat extract microcapsules were determined. The effect of khat extract microcapsules and varying doses of khat extract on sexual motivation in female rats were investigated. Additionally, estradiol levels, vaginal secretions and vaginal pH were determined., Main Outcome Measures: The differences in the effect of khat extract and khat extract microcapsules on sexual motivation, vaginal secretion and estradiol levels in female rats were compared. Results. Cathine and norephedrine were identified in the isolated khat extract at composition of 81.3% and 17.2%, respectively. Among the formulations studied, khat extract microcapsules of formulation 2:3:5 (containing a ratio of khat extract to ovalbumin to gelatin of 2:3:5) were found to exhibit higher yield, loading, and entrapment efficiency. Khat extract microcapsules showed sustained in vitro release and were more stable than khat extract. In addition, khat extract microcapsules enhanced sexual motivation, increased vaginal secretions, and upregulated estradiol level in female rats., Conclusion: The sustained release of alkaloids from dried khat has significantly enhanced the sexual motivation and increased the estradiol level of female rats. Thus the release of dried khat alkaloids from microcapsules might be an effective means of enhancing the libido in females.

Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion-spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.

Curcumin, the main active constituent of turmeric herb (Curcuma longa L.) have been reported to possess many medicinal values. The application of curcumin in dermatological preparations is limited by their intense yellow color property, which stains the fabric and skin. The objectives of this study were to reduce the color staining effect and enhance the stability of curcumin via microencapsulation using gelatin simple coacervation method. As for curcumin, ethanol and acetone were used as coacervating solvents. Curcumin was dispersed in ethanol while dissolved in acetone. Irrespective of the types of coacervating solvents used, microencapsulation resolved the color-staining problem and enhanced the flow properties and photo-stability of curcumin. Nevertheless, it was found that more spherical curcumin microcapsules with higher yield, higher curcumin loading, and higher entrapment efficiency were obtained with acetone than ethanol. The in vitro release of curcumin after microencapsulation was slightly prolonged. Further evaluation of the effects of solubility of core materials in coacervating solvent or polymeric aqueous solution using six different drug compounds, namely, ketoconazole, ketoprofen, magnesium stearate, pseudoephedrine HCl, diclofenac sodium, and paracetamol, suggested that the solubility of core materials in aqueous polymeric solution determined the successful formation of microcapsules. Microcapsules could only be formed if the core materials were not dissolved in the aqueous polymeric solution while the core materials could either be dissolved or dispersed in the coacervating solvent. In summary, microencapsulation not only circumvents the color-staining problem but also improved the stability and flowability of curcumin. The solubility of core material in aqueous polymeric solution plays a pivotal role in determining the successful formation of microcapsules.

Introduction: A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin., Methods: The study method used was a double-blind, two-period, two-treatment, two-sequence, and crossover randomised design. Blood samples were taken before, and within 24 hours after drug administration. Plasma concentrations of ciprofloxacin were determined by a high-performance liquid chromatographic method with ultraviolet detection. The pharmacokinetic parameters, C(max) and T(max), were obtained directly from plasma data, k(e) was estimated by log-linear regression, and the area under the curve (AUC) was calculated by the linear trapezoidal rule. The parameters, AUC(0-infinity) and C(max), were tested for bioequivalence after log-transformation of data, while the differences of T(max) were evaluated nonparametrically., Results: When AUC(0-infinity) and C(max) were analysed using analysis of variance, no statistically significant difference was observed between the two different formulations. The 90 percent confidence intervals of the mean values for the test/reference ratios were 0.95-1.07 for AUC(0-infinity) and 0.90-1.07 for C(max), respectively. Both of these values were within the bioequivalence acceptance range of 0.80-1.25., Conclusion: We found that both formulations are bioequivalent and, therefore, interchangeable.

The potential of using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer to prepare BDP-loaded micelles with high entrapment efficiency and mass median aerodynamic diameter of less than 5 microm demonstrating sustained release properties was evaluated. The result showed that lyophilized BDP-loaded polymeric micelles with entrapment efficiency of more than 96% could be achieved. Entrapment efficiency was affected by both the drug to polymer molar ratio and the amount of drug used. Investigation using FTIR and DSC confirmed that there was no chemical or physical interaction and the drug was molecularly dispersed within the micelles. TEM images showed that the drug-loaded polymeric micelles were spherical in shape with multivesicular morphology. Further analysis by photon correlation spectroscopy indicated that the particle size of the BDP-loaded micelles was about 22 nm in size. In vitro drug release showed a promising sustained release profile over six days following the Higuchi model. The mass median aerodynamic diameter and fine particle fraction were suitable for pulmonary delivery. Moreover, the small amount of deposited drug in the induction port (throat deposition) suggested possible reduction in incidence of oropharyngeal candidiasis, a side effect normally associated with inhaled corticosteroids therapy. The high encapsulation efficiency, comparable inhalation properties, sustained release behavior together with biocompatibility nature of the polymer support the potential of BDP-loaded polymeric micelles as a versatile delivery system to be used in the treatment of asthma and chronic obstructive pulmonary disease.

This paper investigates the use of a neural-network-based intelligent learning system for the prediction of drug release profiles. An experimental study in transdermal iontophoresis (TI) is employed to evaluate the applicability of a particular neural network (NN) model, i.e. the Gaussian mixture model (GMM), in modeling and predicting drug release profiles. A number of tests are systematically designed using the face-centered central composite design (CCD) approach to examine the effects of various process variables simultaneously during the iontophoresis process. The GMM is then applied to model and predict the drug release profiles based on the data samples collected from the experiments. The GMM results are compared with those from multiple regression models. In addition, the bootstrap method is used to assess the reliability of the network predictions by estimating confidence intervals associated with the results. The results demonstrate that the combination of the face-centered CCD and GMM can be employed as a useful intelligent tool for the prediction of time-series profiles in pharmaceutical and biomedical experiments.

Purpose: To investigate the wound healing efficacy of two chitosan films, Chit-AA and Chit-LA, in comparison with a commercial preparation, Omiderm, using punch biopsy wounds in rats., Methods: The punch biopsy wounds were created in the abdominal region of male Wistar rats. The films were evaluated in terms of transparency, flexibility, adherence property, ease of removal from wounds without damaging underlying tissues and fluid accumulation. In addition, the wounds were examined for dryness, exudation, contraction, period of epithelialization and scar formation., Results: Chit-AA, Chit-LA and Omiderm films were comparable in terms of transparency, flexibility, adherence property, ease of film removal from wounds without damaging underlying tissues and fluid accumulation. Although there was no statistically significant difference in wound dryness and exudation between the film treated wounds and untreated wounds (Control), a significant difference was obtained in complete wound closure (t(100%)), period of epithelialization and scar formation., Conclusions: Both Chit-LA and Chit-AA were able to promote wound healing with minimal scar formation.

Applicability of an ensemble of Elman networks with boosting to drug dissolution profile predictions is investigated. Modifications of AdaBoost that enables its use in regression tasks are explained. Two real data sets comprising in vitro dissolution profiles of matrix-controlled-release theophylline pellets are employed to assess the effectiveness of the proposed system. Statistical evaluation and comparison of the results are performed. This work positively demonstrates the potentials of the proposed system for predicting desired drug dissolution characteristics in pharmaceutical product formulation tasks.

Purpose: To investigate and compare the effect of three analytical methods, hydrogen bromide titrimetry (HBr titrimetry), infrared spectroscopy (IR spectroscopy), and first derivative UV-spectrophotometry (FDUV-spectrophotometry) in the determination of degree of deacetylation (DD) of chitosan., Methods: Three different chitosan samples were selected for the DD quantification employing HBR titrimetry, IR spectroscopy with samples in the forms of KBr disc (at ratios of 1:2 and 1:3) and thin film (concentrations of 0.5 percent and 1 percent), and FDUV- spectrophotometry., Results: The mean DD values of chitosan samples obtained by HBr titrimetry was significantly lower (p < 0.05) compared to IR spectroscopy using film (concentrations of 0.5 and 1 percent) as well as FDUV-spectrophotometry (purified and unpurified samples), but were significantly higher (p< 0.005) than those obtained using IR spectroscopy using KBr disk except for Chit-S2 computed using baseline (a), which were closely comparable (p > 0.05). In the IR spectroscopic method, the DD values differed when computed using different baseline. It can be observed that the values calculated using baseline (b) was generally higher than those calculated using baseline (a). On the other hand, chitosan samples prepared in the form of film might not be significantly affected by the different baseline as no consistent trend was observed. For FDUV-spectrophotometry, the DD values of purified Chit-S2 samples dried using oven and freeze dryer were comparable and not significantly different (p > 0.05). Similarly, no significant difference was observed for unpurified chitosan samples when dried using freeze dryer and oven (p > 0.05). Furthermore, the DD values of the purified and unpurified chitosan samples dried using freeze dryer were not significantly different except for Chit-S2., Conclusion: The DD values of chitosan were highly affected by the analytical methods employed. Hence, we proposed that the quantification method for DD should also be stated when reporting the DD value of chitosan sample.

Purpose: To investigate the interpolymer complexation between Carbopol 934P (CP) and various grades of polyvinylpyrrolidone (PVP) (K90, K32, C15, and VA/S-630)., Methods: Amount of fresh and dried CP-PVP complexes, water retaining capacity, apparent density, pH, conductivity, FTIR, swelling and adhesion strength were studied., Results: Interpolymer complexation occurred between CP and all the PVP, but most significantly with PVP K90. Maximum amount of fresh and dried CP-PVP K32 complexes were obtained at a weight ratio of 1:1. On the contrary, CP concentration was linearly related to amount of CP-PVP K90 complexes produced and their water retaining capacity were all above 97%. Increase in CP concentration caused a decrease in pH, but an increase in conductivity for all the CP-PVP complexes. The apparent density of the filtrate of CP-PVP K90 complex was the lowest and its IR spectrum was similar to that of pure PVP K90, indicating that all the CP has interacted with the PVP K90. Discs of physical mixtures of CP-PVP K90 swelled gradually and reached a maximum after 20-30 hr, while discs of solid complex swelled readily and reached a maximum within 20 hr. Adhesion strength was directly correlated to CP content. However, adhesion strength of solid CP-PVP K90 complex was lower than the physical mixture of the pure polymers., Conclusion: Interpolymer complexation occurred between CP and PVP but to a different extent for the various grades of PVP. Complexation was most prominent between CP and PVP K90.

Purpose: To use artificial neural networks for predicting dissolution profiles of matrix-controlled release theophylline pellet preparation, and to evaluate the network performance by comparing the predicted dissolution profiles with those obtained from physical experiments using similarity factor., Methods: The Multi-Layered Perceptron (MLP) neural network was used to predict the dissolution profiles of theophylline pellets containing different ratios of microcrystalline cellulose (MCC) and glyceryl monostearate (GMS). The concepts of leave-one-out as well as a time-point by time-point estimation basis were used to predict the rate of drug release for each matrix ratio. All the data were used for training, except for one set which was selected to compare with the predicted output. The closeness between the predicted and the reference dissolution profiles was investigated using similarity factor (f2)., Results: The f2 values were all above 60, indicating that the predicted dissolution profiles were closely similar to the dissolution profiles obtained from physical experiments., Conclusion: The MLP network could be used as a model for predicting the dissolution profiles of matrix-controlled release theophylline pellet preparation in product development.

This study examined the mechanical (hardness, compressibility, adhesiveness, and cohesiveness) and rheological (zero-rate viscosity and thixotropy) properties of polyethylene glycol (PEG) gels that contain different ratios of Carbopol 934P (CP) and polyvinylpyrrolidone K90 (PVP). Mechanical properties were examined using a texture analyzer (TA-XT2), and rheological properties were examined using a rheometer (Rheomat 115A). In addition, lidocaine release from gels was evaluated using a release apparatus simulating the buccal condition. The results indicated that an increase in CP concentration significantly increased gel compressibility, hardness, and adhesiveness, factors that affect ease of gel removal from container, ease of gel application onto mucosal membrane, and gel bioadhesion. However, CP concentration was negatively correlated with gel cohesiveness, a factor representing structural reformation. In contrast, PVP concentration was negatively correlated with gel hardness and compressibility, but positively correlated with gel cohesiveness. All PEG gels exhibited pseudoplastic flow with thixotropy, indicating a general loss of consistency with increased shearing stress. Drug release T50% was affected by the flow rate of the simulated saliva solution. A reduction in the flow rate caused a slower drug release and hence a higher T50% value. In addition, drug release was significantly reduced as the concentrations of CP and PVP increased because of the increase in zero-rate viscosity of the gels. Response surfaces and contour plots of the dependent variables further substantiated that various combinations of CP and PVP in the PEG gels offered a wide range of mechanical, rheological, and drug-release characteristics. A combination of CP and PVP with complementary physical properties resulted in a prolonged buccal drug delivery.

The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter Cmax was between 0.91 and 1.29. In addition, elimination half-life t1/2 and apparent volume of distribution Vd were calculated. There was no statistically significant difference between the t1/2 Vd values obtained from the data of the two preparations.

Controlled-release grade hydroxypropylmethylcellulose (HPMC) or xanthan gum (XG) and microcrystalline cellulose (MCC) were employed to prepare controlled-release diltiazem hydrochloride tablets. The similarity factor f2 was used for dissolution profile comparison using Herbesser 90 SR as a reference product. Drug release could be sustained in a predictable manner by modifying the content of HPMC or XG. Moreover, the drug release profiles of tablets prepared using these matrix materials were not affected by pH and agitation rate. The f2 values showed that only one batch of tablets (of diltiazem HCl, HPMC or XG, and MCC in proportions of 3.0:3.0:4.0) was considered similar to that of the reference product, with values above 50. The unbiased similarity factor f2* values were not much different from the f2 values, ascribing to a small dissolution variance of the test and reference products. The amount of HPMC or XG incorporated to produce tablets with the desired dissolution profile could be determined from the curves of f2 versus polymer content. Hence, the f2 values can be applied as screening and optimization tools during development of controlled-release preparations.

A simple and selective high-performance liquid chromatography (HPLC) method using ultraviolet detection was developed for simultaneous determination of fusidic acid and betamethasone dipropionate in a cream formulation. A Supelcosil LC18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 0.01 M disodium hydrogen orthophosphate (70:30, % v/v) adjusted to pH 6 with glacial acetic acid. Analysis was run at a flow rate of 1.0 mL/minute with the detector operating at 235 nm. The standard calibration curve was linear over a concentration range of 0.3 to 1.2 mg/mL for fusidic acid and 9.6 to 38.4 micrograms/mL for betamethasone dipropionate. The average recovery values for fusidic acid and betamethasone dipropionate were almost 100%. The within-run and between-run coefficient of variation and percent error values for the two drugs were all less than 2% and +/- 3%, respectively.

Lipophilicity was evaluated as a possible mechanism for drug retardation from a glyceryl monostearate matrix system. Lipophilicity of the glyceryl monostearate matrix system was studied using contact angle measurement of water droplets on the surface of compressed disks, extrudate ascension of water, and movement of water through a powder mixture packed in a high-performance liquid chromatographic (HPLC) column. Increase in glyceryl monostearate content resulted in an increase in water droplet contact angle, decrease in the rate of water ascending the extrudate, and increase in the pressure values as a function of flow rate of water moving through the powder mixture. These could be due to the increase in lipophilicity of the matrix, rendering the matrix less wettable. As a result, the rate of water penetration into the matrix decreased, and the drug release could be sustained.

Purpose: To investigate the suitability of an SCMC (sodium carboxymethyl cellulose/polyethylene glycol 400/carbopol 934P) and an HPMC (hydroxypropylmethyl cellulose/polyethylene glycol 400/carbopol 934P) films as drug vehicle for buccal delivery., Methods: The mechanical and in vitro bioadhesive strength properties of the films were investigated using texture analyzer equipment, while swelling behavior was studied in different media, namely, distilled water and simulated saliva solution. In addition, the in vivo bioadhesion of the film was studied by estimating the film residence time on buccal mucosa of human volunteers., Results: Increase in carbopol 934P content was found to elevate the elasticity, softness and bioadhesive strength but decrease the strength and degree of swelling of both SCMC and HPMC films. SCMC films swelled more extensively in distilled water while HPMC films in simulated saliva solution. HPMC films exhibited greater in vivo bioadhesion although the in vitro bioadhesive strength was lower than SCMC films. Correlation existed between the in vivo and in vitro bioadhesion data within the polymer, but no rank correlation was observed between the two polymers., Conclusion: HPMC films may be preferred over SCMC films as drug vehicle for buccal delivery as the former was tougher, more elastic, more bioadhesive in vivo and swelled in a more tolerable manner in the oral cavity than the latter.

This study was conducted to compare the bioavailability of two controlled-release metformin preparations (Diabetmin Retard and Glucophage Retard) and also to correlate the in vitro and in vivo data obtained with the two preparations. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, time to reach peak plasma concentration Tmax, and peak plasma concentration Cmax, while correlation was determined between in vitro release and in vivo absorption. Diabetmin Retard demonstrated a slower rate of in vitro release, but a faster rate of in vivo absorption than Glucophage Retard. However, the in vivo absorption of both products was found to be slower than that of drug released in vitro. A satisfactory relationship could be established between the in vitro and in vivo results, but there was no rank order correlation. No statistically significant difference was observed between the two preparations in the parameters AUC0-infinity and Cmax. However, a slight but statistically significant difference was observed between the Tmax values, but it may not be therapeutically significant. Moreover, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values, as well as the logarithmic transformed Cmax values, of Diabetmin Retard over those of Glucophage Retard was within the acceptance criteria of 0.80-1.25.

A method using a texture analyzer equipment and chicken pouch as the biological tissue was investigated for measuring the bioadhesive properties of polymers under simulated buccal conditions. The method was evaluated using two polymers, namely Carbopol 974P and Methocel K4M while the instrument variables studied included the contact force, contact time and speed of withdrawal of the probe from the tissue. The parameters measured were the work of adhesion and peak detachment force. Longer contact time and faster probe speed not only gave better reproducibility of results, but also better sensitivities for both parameters measured. On the other hand, a certain level of contact force was found essential for achieving good bioadhesion, above which there was no further contribution to the bioadhesion process. When the method was applied to determine the bioadhesiveness of several polymers, the values obtained for the work of adhesion and peak detachment force were quite consistent in the ranking of the polymers. The Carbopols were found to have the highest values, followed by gelatin, sodium carboxymethyl celluloses and hydroxypropylmethyl celluloses. On the other hand, Alginic acid, Eudragit RLPO and RSPO, and Chitosan appeared to have low bioadhesive values.

The bioavailability of a generic preparation of naltrexone (Narpan) was compared with the innovator product, Trexan. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using the parameters area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the logarithmic transformed AUC0-infinity and the logarithmically transformed Cmax values of the two preparations. Also, no statistically significant difference was observed between the untransformed Tmax values. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of Narpan over those of Trexan was found to lie between 0.87 and 1.01, while that of the logarithmic transformed Cmax values was between 0.94 and 1.23, both being within the bioequivalence limit of 0.80-1.25. The numerical values of the elimination half-life (t1/2) obtained with the two preparations were also not significantly different and were comparable to those reported in the literature.

A study was conducted to compare the bioavailability of a generic product of atenolol (Normaten FC) with the innovator product, Tenormin. Twelve healthy adult volunteers participated in the study conducted according to a randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was obtained between the Tmax values and the logarithmic transformed AUC0-infinity and Cmax values of the two products. Moreover, the 90% confidence interval for the ratio of the logarithmically transformed AUC0-infinity values of Normaten FC over those of Tenormin was found to lie between 0.82 and 0.98, while that of the logarithmically transformed Cmax values was between 0.82 and 1.09, both being within the bioequivalence limit of 0.80-1.25. The values of elimination half-life t1/2 between the two products were also found comparable and not significantly different statistically. The t1/2 values obtained in our study were slightly longer than those reported in the literature for other population groups.

Controlled release buccal patches were fabricated using Eudragit NE40D and studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose and Carbopol of different grades, were incorporated into the patches, to modify their bioadhesive properties as well as the rate of drug release, using metoprolol tartrate as the model drug. The in-vitro drug release was determined using the USP 23 dissolution test apparatus 5 with slight modification, while the bioadhesive properties were evaluated using texture analyzer equipment with chicken pouch as the model tissue. The incorporation of hydrophilic polymers was found to affect the drug release as well as enhance the bioadhesiveness. Although high viscosity polymers can enhance the bioadhesiveness of the patches, they also tend to cause non-homogeneous distribution of the polymers and drug, resulting in non-predictable drug-release rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most satisfactory in terms of modifying the drug release and enhancement of the bioadhesive properties.

A simple high-performance liquid chromatographic method was developed for the determination of ranitidine in human plasma. Prior to analysis, ranitidine and the internal standard (metoprolol) were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M potassium dihydrogenphosphate-acetonitrile (88:12, v/v) adjusted to pH 6.5. Analysis was run at a flow-rate of 1.3 ml/min and at a detection wavelength of 229 nm. The method is sensitive with a detection limit of 1 ng/ml at a signal-to-noise ratio of 3:1, while the quantification limit was set at 15 ng/ml. The calibration curve was linear over a concentration range of 15-2000 ng/ml. Mean recovery value of the extraction procedure was about 90%, while the within-day and between-day coefficients of variation and percent error values of the assay method were all less than 15%.

A study was conducted to compare the in vivo bioavailability of a generic metoprolol tablet preparation (Metoprolol) with that of the innovator product, Betaloc. Both preparations have a labeled dose of 100 mg metoprolol tartrate. Twelve healthy adult male volunteers participated in the study, which was conducted according to a standard two-way crossover design with a washout period of 1 week. The bioavailability was compared using the total area under the plasma level versus time curve (AUC0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the logarithmically transformed AUC0-infinity values or the logarithmically transformed Cmax values of the two preparations. However, a statistically significant difference was observed between the Tmax values, but may not be therapeutically significant or important. Moreover, the 90% confidence interval (CI) for the ratio of the logarithmically transformed AUC0-infinity values of Metoprolol over those of Betaloc was calculated to be between 0.94 and 1.02, while that of Cmax was between 0.98 and 1.01, both of which are within the acceptable limit of 0.80-1.25. From the data obtained, it was also observed that a high proportion of our volunteers of Asian origin appeared to be poor metabolizers of metoprolol, which was consistent with what had been observed in our previous study of another preparation of metoprolol.

A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of ketoconazole in human plasma. The method entailed direct injection of the plasma sample after deproteinization using acetonitrile. The mobile phase comprised 0.05 M disodium hydrogen orthophosphate and acetonitrile (50:50, v/v) adjusted to pH 6. Analysis was run at a flow-rate of 1.5 ml/min with the detector operating at an excitation wavelength of 260 nm and an emission wavelength of 375 nm. The method is specific and sensitive with a quantification limit of approximately 60 ng/ml and a detection limit of 40 ng/ml at a signal-to-noise ratio of 3:1. Mean absolute recovery value was about 105%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 14%. The calibration curve was linear over a concentration range of 62.5-8000 ng/ml.

The bioavailability of a generic preparation of acyclovir (Avorax) was compared with the innovator product, Zovirax. Twelve healthy volunteers participated in the study, conducted according to a randomized, two-way crossover design. The preparations were compared using the parameters area under the plasma concentration time curve (AUC(0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the Tmax or the logarithmic transformed AUC(0-infinity) and C(max) values of the two preparations. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC(0-infinity) values of Avorax over those of Zovirax was found to lie between 0.85 and 1.06, while that of the logarithmic transformed Cmax values was between 0.95 and 1.25, being within the bioequivalence limit of 0.80-1.25. Moreover, the elimination rate constant (k(e)), elimination half-life (t(1/2)), and apparent volume of distribution (Vd) values obtained with the two preparations were comparable and not significantly different statistically.

Ethyl acrylate-methyl methacrylate copolymer (Eudragit NE40D) was evaluated as matrix material for preparing controlled-release tablets of diclofenac sodium. Drug release could be modified in a predictable manner by varying the Eudragit NE40D content, but was pH dependent, being markedly reduced at lower pH. This could be attributed to the low solubility of the drug at these pH values. Thermal treatment of the tablets at 60 degrees C was also found to affect the rate of drug release, which was found to decrease with an increase in the treatment duration, but could be stabilized after 96 hr of treatment. This was also associated with a corresponding increase in the tablet tensile strength. However, treatment of the granules for 5 hr prior to compaction into tablets could shorten the stabilizing time of the drug release to 48 hr and that of the tensile strength to 24 hr. The effect of thermal treatment may be ascribed to better coalescence of the Eudragit particles to form a fine network, resulting in matrix of higher tortuosity and lower porosity.

A simple liquid chromatographic method using amperometric detection was developed for the determination of naltrexone in human plasma. Prior to analysis, naltrexone and the internal standard (naloxone) were extracted from plasma samples using a 9:1 mixture of chloroform and isopropyl alcohol. The mobile phase comprised 0.1 M disodium hydrogen orthophosphate (pH 3.5) and acetonitrile (85.5:14.5, v/v). Analysis was run at a flow-rate of 0.8 ml/min with the detector operating under oxidative mode at an applied potential of +0.95 V. The method is specific and sensitive with a detection limit of approximately 1 ng/ml at a signal-to-noise ratio of 3:1. Mean recovery value of the extraction procedure was about 93%, while the within day and between day coefficient of variation and percent error values of the assay method were all less than 10%. The calibration curve was linear over a concentration range of 1.5-100 ng/ml.

A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of acyclovir in human plasma. The method entailed direct injection of the plasma sample after deproteination. It is both specific and sensitive with a detection limit of 30 ng/ml at a signal-to-noise ratio of 3:1, and is thus suitable for use in pharmacokinetic studies of acyclovir. The method had a mean absolute recovery of 96%, while the within-day and between-day coefficients of variation and percentages error were all less than 8%. The calibration curve was linear over a concentration range of 62.5-4000 ng/ml.

A high-performance liquid chromatography assay equipped with a glassy carbon electrode for electrochemical detection (HPLC-ECD) was developed at reductive mode for the analysis of artemisinin, the antimalarial drug from Artemisia annua (Asteraceae) in human plasma. This method was selective, sensitive, and produced satisfactory recovery, precision, and accuracy. Analysis of plasma samples from 8 male volunteers given 10 mg kg-1 of artemisinin orally as an aqueous suspension showed a mean peak plasma concentration (Cmax) of 580.89 ng ml-1 +/- 88.64 SD at 2.5 h +/- 0.5 SD after dosing, and the mean area under the plasma concentration-time curve (AUC0-infinity) was 2227.57 ng h ml-1 +/- 677.22 SD. In addition, the elimination rate constant (Ke), elimination half-life (t1/2), and apparent volume of distribution (Vd) were calculated to be 0.2971 h-1 +/- 0.0644 SD, 2.42 h +/- 0.46 SD, and 16.26 l kg-1 +/- 3.44 SD, respectively.