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The major oral solid medicines are sold in blister and strips packaging, which are packaged in a carton box. Children, who manage to open such boxes, while unsupervised, are in great danger of being poisoned by swallowing the contents. A CRP usually requires a special trick to open it. The aim was to design and validate the performance of innovative CRP system with unique features. Materials used were the plastic grade, click lock system, and blister pack. The test conducted on test panels of 100 healthy children between 42 and 51 months were asked to open a pack. Each panel divided into 3 groups, viz. 30 children of 42–44 months, 40 children 45–48 months, and 30 children 49–51 months. The panel of 100 healthy adults divided into 3 groups, viz. 25 adults 18–40 years, 25 adults 40–59 years, and 50 adults 60–70 years. Results shown only 6% of children succeeded to open CRP, while 94% failed to open CRP within 5 min. In the case of adults, 96% succeeded to open CRP without imposing any difficulties. There was a successful development of a prototype of CRP, which can used for the packaging of pharmaceutical products. CRP deprived children to have access of medicated packaging system, which resulted in devoid of any poisonous effect to the children.

The objective of the present study was to identify critical formulation parameters affecting the drug release from modified release wax matrix tablet of milnacipran hydrochloride employing the concept of design of experiments.The optimized amount of Compritol 888 ATO(intragranular) (X1), lactose (X2) and Compritol 888ATO (extragranular)(X3) were determined employing simplex latticedesign. The tablets were prepared using melt granulation technique. The in vitro drug release study was carried out in an acidic medium (pH 1.2) for 2 h and thereafter the dissolution study was conducted in phosphate buffer (pH 6.8).The selected dependent variables were the cumulative percentage of milnacipran hydrochloride dissolved at 1 (Y1), 8 (Y8), 16 (Y16) and 24 h (Y24). Mathematical models, correlating the independent variables with dependent variables were evolved. Optimization was performed for the three independent variables using the stated target ranges; Y1≤20%; Y8=45±5%; Y16=72±5%; Y24=100%. The optimized amounts of Compritol ATO888 (intragranular)(X1), lactose (X2) and Compritol 888ATO (extragranular)(X3), were found to be 60, 55 and 30 mg, respectively.The optimized formulation showed a release profile that was close to the predicted values. The drug was released by anomalous diffusion from the optimized formulation. Compritol 888ATO (intragranular) (X1), lactose (X2) and Compritol 888ATO(extragranular) (X3) were identified as critical variables.

The present research work was undertaken to formulate modified release tablets of lornoxicam using Compritol 888 ATO as a lipid matrixing agent and to evaluate the tablets for dissolution in hydro-alcoholic dissolution media to meet the requirement of regulators. The dissolution study was also conducted in aqueous medium containing alcohol and hydroxylpropyl methylcellulose to mimic the viscosity and pH after food and alcohol intake. The tablets were prepared by direct compression by adopting the concept of design of experiments and evaluated mainly for dissolution studies in aqueous dissolution media containing 10, 25 and 40% ethyl alcohol. The formulated tablets satisfied the USP requirements of drug release at 2, 6 and 10 hr. The drug release was insignificantly altered when the dissolution study was conducted in media containing increasing amount of alcohol probably due to higher solubility of the drug in alcohol. The drug release was suppressed when HPMC was used in the dissolution media. This may be due to rise in viscosity of the dissolution media. Dose dumping was not noticed under the experimental conditions.

The present study was carried out with an aim to improve dissolution rate of febuxostat (FBX, BCSclass II) drug. Spherical agglomerates were prepared by hybrid technique of spherical crystallization and solid dispersion using different ratios of FBX and polymer (PVP K30, HPMC E3LV and chitosan). Drug excipient compatibility study was evaluated by Fourier transform infrared spectroscopy and X-ray diffractometry. Scanning electron microscopy was used for measurement of size of agglomerate. In vitro dissolution study of prepared spherical agglomerates was compared with untreated FBX and marketed formulation in phosphate buffer pH 6.8. The ratio of drug to polymer also affected the drug dissolution results. Drug excipient compatibility study showed no interaction between FBX and PVP K30 (1:5) polymer. The use of PVP K30 (1:5) resulted in partial amorphization and improved drug dissolution. Direct compression method can be adopted in manufacturing to simplify the validation efforts. The performance of the formulated product was superior to the marketed product in the in vitro dissolution test.

In current study, a nanoemulsion as drug delivery system (NE) of spray dried Boswellia Serrata Extract (BSE) was developed and characterized to compare it in vitro/Ex vivo diffusion with reference formulation. Pseudo-ternary phase diagrams were constructed by phase diagram by aqueous titration method, of which the evaluation method was improved for solubility, Droplet size and transmittance. The formulation of BSE-loaded NE was optimized by a Simplex lattice mixture experimental design. The optimized nanoemulsion formulation, loading with 199.8 mg g-1 BSE total boswellic acids, consisted of Isopropyl Myristate, Tween 80 and Ethanol (2:8:10, w/w) and it remained stable after storing at 40°C, 25°C, 4°C for at least 6 months. When diluted with water, the NE droplet size was 11.25 nm and the zeta potential was 0.223 mV. The spherical droplet shape was confirmed by TEM analysis. Ex vivo skin permeation and in vivo anti-inflammatory study were conducted. About 3.25 fold increase in flux was seen in case of nanoemulsion, nanogel showed 1.45 fold increase in flux as compared to carbopol gel with highest enhancement ratio 4.57 and 1.59 respectively. Our study illustrated potential of developed nanoemulsion as possible alternative to traditional topical formulations.

The drug-excipient compatibility study of quetiapine fumarate, with widely used sustained release excipients, was carried out employing differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The selected excipients were HPMC K100M, sodium alginate, xanthan gum, Eudragit RSPO, hydrogenated castor oil, carnauba wax, and PEO WSR 303. Equal proportion of drug and excipients was utilized in the interaction study. FT-IR spectra indicated the absence of interaction between drug and excipients. The DSC curve showed a sharp endothermic melting peak at 173.26 °C for quetiapine fumarate. Post melting interaction was observed for carnauba wax, Eudragit RSPO, and hydrogenated castor oil probably due to solubilization of drug in the melted excipient. No interaction was observed for other excipients. The physical mixtures stored at 30 ± 2 °C/65 ± 5% RH did not show any significant degradation of the drug. The concept of systemically conducted preformulation studies will facilitate dossier submission to the drug control authority.

The present study was carried out with a view to enhance dissolution rate of poorly water-soluble drug aceclofenac (BCS-class II) using Avicel 200 and Sylysia 350 as polymers. Surface solid dispersion (SSD) was prepared by kneading method using different ratios of aceclofenac and polymers. Phase solubility study was conducted to evaluate the effect of polymer on aqueous solubility of aceclofenac. Solid state characterization was evaluated by Scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD). In vitro dissolution study was performed in phosphate buffer at pH 6.8. Solid state study showed partial interaction between aceclofenac and polymer. In vitro dissolution rate of aceclofenac from solid dispersion (SD) was significantly higher compared to pure aceclofenac. The dissolution rate of the drug was affected by nature and amount of polymer used. The dissolution rate of aceclofenac/Avicel 200 solid dispersion (1:5) was higher than that of aceclofenac/Sylysia 350 solid dispersion (1:3). Thus, solid dispersion technique can be successfully used for the improvement of the dissolution profile of aceclofenac.

Purpose: With the introduction of combinatorial chemistry and high throughput screening, the properties of new chemical entities shifted towards higher molecular weight and increasing lipophilicity that results in decreasing aqueous solubility. It is not surprising that many drug candidates have poor water solubility since the initial selection of drug candidates are based on activity alone. Other physiochemical and biopharmaceutical properties such as permeability, biopharmaceutics and metabolism are rarely considered during the selection process. The aim of this study was to increase dissolution rate of felodipine poorly soluble drugs from BCS class II by complexation process. Methods: Complexation was prepared using cyclodextrine. Different techniques were employed for preparation of complexation with cyclodextrin like physical mixture, cogrinding, kneading technology, solvent coevaporation. Results and Conclusions: The physical properties of the prepared solid mass of FDP was characterized by in vitro dissolution studies, UV- spectroscopy, Fourior transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray powder differaction spectroscopy. Additionaly, phase solubility studies were performed to support the in vitro dissolution study. The results of Fourior transform infrared spectroscopy shows the compatibility of drug with cyclodextrin, while differential scanning calorimetry (DSC) and X-ray powder differaction spectroscopy showed the confirmation of complexation of cyclodextrin with felodipine. © 2011 IGJPS. All rights reserved

The objective of this work was to develop floating levofloxacin tablets and to understand the kinetics of drug release by applying mathematical and model-dependent approaches. Nine formulations of floating tablets were prepared by the direct compression method using Gelucire 43/01 (hydrophobic) and hydroxypropyl methylcellulose (hydrophilic) as matrix-forming excipients. The in vitro drug release was studied in pH 1.2 HCl using USP dissolution Apparatus 2 at 50 rpm. Zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer et al. models were used to estimate the kinetics of drug release. The criteria for selecting the most appropriate model were based on the goodness-of-fit test and lowest sum of squares residual. Drug release from the optimal batch was explained by the Higuchi model. A simple mathematical approach was applied to determine the deviation in area under the curve (AUC) between predicated and observed dissolution data. The difference in percent deviation of AUC at each point was lowest for the optimum batch. Drug release was a function of the ratio of hydrophobic to hydrophilic matrixing agent.

Context: Transdermal spray (TS) of clotrimazole (CTZ) was formulated to improve the drug transport through the skin up to 12 h to achieve the antifungal efficacy. Objective: The aim of present study was to formulate and evaluate antifungal transdermal spray to improve the permeation of clotrimazole across the skin and to decrease the dosing frequency in fungal infection. Materials and methods: Different ratios of ethanol and acetone and various grades of eudragit and ethyl cellulose were evaluated according to six criteria: viscosity, drying time, stickiness, appearance and integrity on skin and water washability. Propylene glycol (PG) and polyethylene glycol 400 (PEG 400) were used in the study as plasticizer and solubilizer. The TS was evaluated for in vitro drug release, spray angle, spray pattern, average weight per dose, pH, drug content, evaporation time, leak test and antifungal efficacy study. Results and discussion: Eudragit E100 and blend of ethanol and acetone (80:20) satisfied the desired criteria. The selection of optimized batch was based on the results of in vitro drug release, spray pattern and spray angle. The optimized batch showed the spray angle Conclusion: The TS of CTZ can be an innovative and promising approach for the topical administration in the fungal diseases.

A co-grinding method was used to improve the dissolution characteristics of nimesulide, a poorly water-soluble non-steroidal anti-inflammatory drug. Nimesulide solubility was studied to determine the solubilization process using different concentrations of Tween 80 at different pH values. At a 10% Tween 80 concentration, a large proportion (> 90%) of drug was entrapped in micelles when the pH of buffer solution was greater than pKa of nimesulide. A 32 factorial design was adopted using the concentration of Tween 80 and sodium lauryl sulphate as independent variables. Improved drug dissolution was obtained when the drug was mixed first with aqueous surfactant solution and later blended with adjuvant such as lactose and microcrystalline cellulose. Sodium lauryl sulphate was more effective in increasing the drug dissolution compared with Tween 80. The use of a blend of Tween 80 and sodium lauryl sulphate is justified since the interaction term (Tween 80 x sodium lauryl sulphate) for percentage drug release in 45 and 120 min was not significant. Contour plots were obtained for the angle of repose and percentage drug release in 30, 45 and 120 min. The study revealed that optimum level of surfactants should be used. The granule flow was adversely affected and no further improvement of drug dissolution was observed when the surfactants were used at high levels. The improved drug dissolution may be attributed to improved wetting and micellization due to presence of surfactants or hydrophilic adjuvant. More than two-fold increase in the drug dissolution was obtained by the selected batches.

The purpose of this study was to develop sustained-release tablets of diltiazem HCl using alkali-treated guar gum as a hydrophilic matrixing agent. The effect of NaOH concentration on swelling of modified guar gum was more pronounced than that of time and temperature. The tablets of diltiazem HCl, containing either untreated or modified guar gum, were compared in terms of drug dissolution, matrix erosion and hydration. The drug release profile of the tablets containing untreated guar gum showed a tailing effect in the terminal phase, which was not observed in the tablets containing modified guar gum. Poor correlation was found between erosion and drug dissolution. The tablets swelled considerably during the hydration study. A uniform precision rotatable central composite design was used to investigate the influence of the amount of diltiazem HCl, modified guar gum and succinic acid on in-vitro drug dissolution. Interactive polynomial models were evolved for the time required for 63.2(t63.2) and 80% (t80) drug release. Response surface plots were generated to show the effect of formulation variables on t63.2. A polynomial equation was also derived for prediction of the drug release profile. An ideal formulation was selected by applying various constraints such as t63.2, t80 and percentage drug released in 60, 360, 540 and 720 min. The kinetics of drug release fitted the Weibull model. It was concluded that modified guar gum could be used as an economical hydrophilic matrixing agent for the formulation of sustained-release tablets of diltiazem HCl.

The present study deals with the preparation of microspheres of diclofenac sodium using cross-linked poly(vinyl alcohol) (PVA). A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for developing the microspheres. The PVA to the drug ratio X1 and amount of glutaral-dehyde cross-linking agent X2 were chosen as the independent variables. The time required for 50% drug dissolution t50 in phosphate buffer (pH 7.2) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable t50. Based on the results of multiple linear regression analysis and F statistics, it may be concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. A response surface plot is presented to show the effects of X1 and X2 on t50. The drug release pattern fit the Higuchi model well. A model was validated for accurate prediction of the drug dissolution profile with constraints on the percentage drug release in the first, fifth, and seventh hours. The data of a selected batch were subjected to an optimization study, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

The purpose of this study was to develop modified-release tablets of diltiazem hydrochloride using physically modified ispaghula husk as a hydrophilic matrixing agent. Ispaghula husk and water were exposed to heat in a hot air oven or microwave oven. The treated samples were evaluated for swelling and rigid gel formation. Microwave oven treated samples showed rigid gel formation and hence they were systematically studied using 32 factorial design using heating time and amount of water as independent variables. Diltiazem tablets were prepared using treated samples and analyzed for in vitro drug release. A polynomial equation was generated using statistically significant terms such as heating time, X1, amount of water, X2, and X1X2 and X12 for predicting time required for 80% drug dissolution. Heating time was found to have a predominant effect in sustaining the drug release. A contour plot is presented for interpretation of the results. The tablets exhibited more axial swelling than radial swelling...

Seven batches of poly(D, L-lactic acid) (PLA) were prepared from D, L-lactic acid using tetraphenyltin or zinc acetate as a catalyst. The samples of PLA were characterized by terminal group analysis, gel permeation chromatography, infrared analysis, and differential scanning calorimetry. Polymerization conditions such as the time of reaction and the type of catalyst affected the molecular weight of PLA. Microspheres containing indomethacin were prepared by the oil/water (o/w) solvent evaporation technique using different formulations and process variables. The in vitro release of indornethacin in phosphate buffer was found to be dependent on the molecular weight of PLA and also on the type and amount of adjuvants used. The batch of microspheres containing 5% cholesterol released the drug at a slow controlled rate (29%, 65%. and 85% in 1, 7, and 24 hr, respectively). The results of F test for the microspheres revealed that there is no significant direrence between the Higuchi model and the power la...

The objective of present work was to construct nomogram for obtaining a value of similarity factor (f2) by employing the values of number of observations (n) and sum of squared difference of percentage drug dissolved between reference (R) and test (T) products . The steps for rearrangement of equation of similarity factor are presented. The values of f2 were selected in the range of 45 to 100 for 4 to 12 observations (n) for computing the values of Linear regression analysis was performed between number of observations and . Perfect correlation was observed in each case. Nomogram was constructed and later it was validated by using drug dissolution data from literature and our laboratory. The use of nomogram is recommended during research and development work to investigate effect of formulation or process variables. The nomogram can also be used during change in manufacturing site or change in equipment. It is concluded that the steps for calculation of f2 can be truncated in the middle (i.e. at the step of calculation of factor and a decision of similarity/dissimilarity can be taken employing the nomogram.

Ethyl cellulose pseudolatices were prepared by an emulsion-solvent evaporation technique, which consisted of dissolving the polymer in a blend of benzene and ethyl alcohol, followed by the addition of adjuvants. The organic, solvents were removed from the emulsion using vacuum distillation. Physical evaluation of the dispersions and the cast films was carried out.On the basis of characteristics of cast films selected formulations were fused as granulating agents for preparing chlorpheniramine maleate tablets. Good correlation was observed between total solid in the granulating dispersion and the drug release. The possible mechanisms for the drug release from the tablets are suggested.

Direct compression is the preferred method for the preparation of tablets. The present review outlines the importance of the functionality of the directly compressible adjuvants in the formulation of tablets. The co-processing is the most widely explored method for the preparation of directly compressible adjuvants because it is cost effective and can be prepared in-house based on the functionality required. Hence, the present review focuses on the properties of the co-processed directly compressible adjuvants available in the market.

(Hydroxypropyl)methyl cellulose and xanthan gum were used as hydrophilic matrixing agents for preparing modified release tablets of diltiazem HCl. The amount of (Hydroxypropyl)methyl cellulose and xanthan gum exhibited significant effect on drug release from the tablets prepared by direct compression technique. Xanthan gum showed a higher ability to retard the drug release than (Hydroxypropyl)methyl cellulose. A 2(2) + 1 factorial design was adopted to study the effect of amount of (Hydroxypropyl)methyl cellulose and xanthan gum on percent drug released in first hour (Y60) and the time required for 90% drug dissolution (t90). A response surface plot is generated for investigating the effect of the independent variables on t90. The tablets containing 90 mg diltiazem HCl, 45 mg (Hydroxypropyl)methyl cellulose and 45 mg xanthan gum showed drug release upto 12 h. The value of similarity factor, f2, for the selected batch was found to be 85.1 when the dissolution study was carried out in water or simulated gastric fluid, indicating pH independent drug dissolution. The selected batch also showed a comparable release profile with a market product (f2 = 60.2). Linear relationship was observed between percent drug released and degree of swelling. The kinetics of the drug release fitted well to the Hixson-Crowell equation. It can be concluded that by using a suitable blend of (Hydroxypropyl)methyl cellulose and xanthan gum desired modified drug release can be achieved.

The objective of this study was to develop modified-release tablets of diltiazem HCl using a direct compression technique. A 3(2) factorial design was employed using the amount of alkali-treated guar gum and cetyl alcohol as independent variables. This article proposes the use of a novel approach-f2 and Sd values as dependent variables-to evaluate the effect of selected independent variables along with other dependent variables (i.e., percentage drug released in x min, Yx; time required for z% drug release, tz; and mean dissolution time (MDT)). It is concluded that when a decision is to be made for the selection of a best batch, it is perhaps more realistic to use the f2 or Sd value which takes into account the dissolution profile as a whole, as opposed to Yx and tz values which use just one point from the dissolution plot. The batch showing the f2 value nearest to 100 or the Sd value nearest to zero is ranked as the best batch (diltiazem HCl 90 mg, alkali-treated guar gum 80 mg and cetyl alcohol 15 mg). The gel strength and matrix erosion of the formulated tablets were dependent on the type and amount of the adjuvants. The drug release rate is well correlated with matrix erosion. The kinetics of drug release fitted best to the Korsmeyer and Peppas model. It is concluded that by using a proper combination of the hydrophilic polymer and cetyl alcohol one can achieve a desirable drug release pattern.

The aim of the present investigation was to develop oral films of valdecoxib using Eudragit EPO and hydroxypropylmethylcellulose. Films of Eudragit EPO, hydroxypropylmethylcellulose and Eudragit EPO combined with hydroxypropylmethylcellulose were prepared by film casting method. Glycerol, menthol and aspartame were incorporated in the drug containing films as plasticizer, cooling agent and sweetener, respectively. The drug loading was 10 mg valdecoxib per 4 cm2 of the film. The films were evaluated for hydration study, folding endurance and in vitro drug dissolution in the distilled water. The films containing both Eudragit EPO and hydroxypropylmethylcellulose films showed neutral surface pH when prepared using 0.1 N HCl as a solvent. Glycerol played a critical role in imparting flexibility to the film and improving the drug release from film. The bitter taste of the drug was masked by using aspartame and menthol accompanied by the synergistic effect of Eudragit and glycerol. Water uptake by films was found to be dependant both on the amount of Eudragit EPO and glycerol. The films containing the higher proportion of glycerol showed higher water uptake and faster drug release at all the sampling time in the in vitro dissolution test. Optimum plasticity was obtained using the required concentration of hydroxypropylmethylcellulose and glycerol. The study revealed that taste masked valdecoxib films can be developed by the selection of appropriate film former and by the use of auxiliary excipients.

Withaferin A, a steroidal lactone which is present in dry root extract of Withania somnifera (WSE), is reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study is to enhance the dissolution rate and oral bioavailability of WSE by incorporating it in self nano emulsifying drug delivery system (SNEDDS). Capmul MCM-based SNEDDS formulation with Tween 20 as surfactant and ethanol as co surfactant was developed for oral delivery of withaferin A. Optimised SNEDDS was evaluated for its self-emulsification time and viscosity, droplet size. The optimised SNEDDS formulation containing withaferin A, Capmul MCM(12.4%), Tween 20 (58.2%) and ethanol (29%), and showed higher in vitro drug release as compared to pure WSE. These results demonstrate the potential use of SNEDDS for improving the oral bioavailability of poor water soluble compounds such as withaferin A.

Ratio derivative spectrophotometric method has been developed for the simultaneous determination of artemisinin and curcumin. The overlapping spectra of both drugs were resolved by making use of the first-derivative of the ratios of their direct absorption spectra. The derivative ratio absorbances of artemisinin and curcumin were measured at λmax 293.17 and λmax 457.0 nm, respectively, for their quantification. Artemisinin and curcumin were determined in the concentration range of 2-10 μg/mL and 1-5 μg/mL, respectively. The method was validated as per the ICH guidelines and accuracy, precision were found to be within acceptable limit. The limits of detection and quantitation were found to be 0.003299 and 0.009997 μg/mL, respectively for artemisinin and 0.006743 and 0.020434 μg/mL, respectively for curcumin. The proposed ratio first derivative spectrophotometric method is novel, rapid, simple, sensitive, accurate, precise and successfully applicable for simultaneous estimation of artemisinin and curcumin in parentral dosage form.