Factorial Batches Research Articles

Study on the influence degree of variables of gangue entrainment in low-rank coal flotation

ABSTRACT In high-ash low-rank coal flotation, often the entrainment of kaolinite (a gangue mineral) seriously affects the quality of the concentrate. Entrainment in flotation is a complex process. Literature suggests that operating conditions have a significant impact on the degree of entrainment. In this study, a factorial batch flotation experiment, using a mixture of low-rank coal and pure kaolinite, was performed to investigate the effects of each factor and the interaction between two factors of these variables (including air rate, impeller speed, pulp density and frother dosage) on the entrainment of gangue mineral. The results show that both the air rate and impeller speed highly significantly affect the gangue entrainment and water recovery. Pulp density interacted with both the impeller speed and frother dosage, having a statistically significant effect on the degree of entrainment. Moreover, the interaction between pulp density and frother dosage had a significant impact on gangue entrainment recovery. Besides, water recovery was significantly influenced by the interaction between the air rate and frother dosage.

Phyto-cosmeceutical gel containing curcumin and quercetin loaded mixed micelles for improved anti-oxidant and photoprotective activity

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0–30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.

Microwave Irradiation Technique: A Green Chemistry Approach for Dissolution Enhancement of Ritonavir

This research was focused on improvement of aqueous solubility of Ritonavir (RIT), Antiretroviral (ART) drug by preparing solid dispersion (SD) through solvent methodology and microwave irradiation (MWI) technique as a green chemistry approach. In MWI different batches of SD were formulated by 32 factorial approach with time of exposure (X1) and power of radiation (X2) as variable quantity and dissolution rate as response (Y1). β-CD was used as hydrophilic carriers. Drug carrier magnitude relation of 1:1 resolve by phase solubility analysis and SD were assessed for drug content, percentage dissolution rate studies, FTIR, XRD, DSC and SEM analysis. The FTIR, XRD, DSC and SEM studies exhibited no interaction between RIT and excipient. In Physical mixture (PM) it shows less intensity and disappearance of sharp peaks while in SD indicates the conversion of crystalline state of RIT to amorphous state that discovered the dissolution enhancing, so the SD prepared by MWI proved to be a promising approach to increasing the dissolving rate of BCS class II drug RIT. Hence, from the all analysis studies, it absolutely was evident that factorial batch F2 was the higher. F2 coded batch (RIT: β-CD within the magnitude relation of 1:1 with time of exposure (4 min) and power of radiation (450 Watt), shows 06 folds increase i.e. 58% compared with drug discharged inside 60 min to plane RIT and SD i.e. 9 % only and 47 % respectively.

Relationship between soil CO2 fluxes and soil moisture: Anaerobic sources explain fluxes at high water content

Soil moisture is a known environmental factor influencing carbon dioxide (CO2) emissions and therefore represents an important variable in predictive models. Establishing relationships between soil CO2 emissions and soil moisture has long focused on the role of soil organic carbon mineralization by aerobic respiration. This approach, which generally yields a bell-shaped relationship establishing maximum CO2 production at moderate soil moisture, ignores anaerobic processes as a potential source of CO2. To decouple the effects of soil moisture and O2, we conducted a factorial batch experiment by incubating soil samples at different imposed moisture contents (30%, 45%, 65%, 80%, and 100% water-filled pore space; WFPS) at 25 °C, under both oxic (normal air) and anoxic (N2 atmosphere) headspace conditions. Gas fluxes measured in the oxic incubations show that CO2 fluxes were maximal (31.2 ± 1.8 nmol cm−3 soil hr-1) at moderate moisture content (65% WFPS), as commonly reported. However, contrary to previous models that predict negligible CO2 fluxes under fully saturated conditions due to O2 limitation, substantial fluxes of CO2 (18.1 ± 2.2 nmol cm−3 soil hr-1) were measured at 100% WFPS. In the anoxic treatments, CO2 fluxes rose sharply when the moisture content exceeded 65% WFPS, with values at 100% saturation (21.8 ± 2.2 nmol cm−3 soil hr-1), close to the corresponding fluxes in the oxic incubations. Methane (CH4) fluxes in the anoxic incubations increased over time, ultimately reaching parity with the CO2 fluxes at 100% WFPS. To reproduce the soil moisture dependence of the CO2 fluxes, we propose a kinetic model representing both aerobic and anaerobic CO2 production. Together, the gas flux measurements, porewater geochemistry data, and modeling results indicated that at soil moisture contents approaching saturation (≥90%), anaerobic processes were the major source of CO2 in the oxic incubations. Overall, we conclude that existing models may underrepresent soil CO2 production at high soil moisture by not considering anaerobic reaction pathways releasing CO2.

Formulation Development and Evaluation of Mucoadhesive Buccal Tablets of Acebutolol Hydrochloride

A mucoadhesive drug delivery system is an oral dosage form, where the tablet, gel, or patch is attached to the buccal region for direct absorption of the drug into blood circulation. This dosage form has been employed to improve the bioavailability of drugs that undergoes significant hepatic first-pass metabolism. Acebutolol is a beta sympatholytic agent used to treat high blood pressure and irregular heartbeat (arrhythmia). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. In present investigation, mucoadhesive buccal tablets of acebutolol HCl were prepared using carbopol 940 in varying concentrations with secondary polymer xanthan gum by direct compression method. Nine batches were prepared as per 32 factorial designs, to investigate the combined effects of independent variables namely carbopol 940 and xanthan gum on dependant variables namely swelling index, mucoadhesion strength and in-vitro drug release using design expert software version 8.0.7.1. Preformulation studies confirmed the identity and purity of the drug by means of UV spectroscopy, IR spectroscopy, DSC analysis, and melting point determination. The tablets were evaluated for hardness, thickness, weight variation, friability, and drug content concluded that all these parameters were in an acceptable range of pharmacopoeial specification. The buccal tablets were studied for surface pH, swelling index, in vitro drug release study, adhesion force, in vitro mucoadhesive strength, stability, and compatibility study to optimise the formula. Amongst all factorial batches (F1 to F9), batch F5 (30 mg carbopol 940 and 30 mg xanthan gum) showed maximum drug release of 99.96 % after 12 hr of study and also showed better contact with biological membrane. The drug release kinetics of batch F5 was found to be best fitted to zero order kinetic model and exhibited anomalous diffusion release mechanism. The formulation F5 exhibited good correlation (R2=0.992) for in-vitro drug release. All the evaluation parameters give positive results and comply with the standards. Stability studies were carried out on the developed formulations indicating that the formulations were stable during the period of 6 months. In conclusion, the formulation F5 is stable and effective for quick action and seems to be alternative to the conventional tablet.

Microwave Irradiation Technique, a Green Chemistry Approach for Dissolution Enhancement of Lopinavir

Aim: This research was focused on improvement of aqueous solubility of Lopinavir (LPO), Antiretroviral (ART) drug by preparing solid dispersion (SD) through microwave irradiation (MWI) technique as a green chemistry approach.
 Place and Duration of Study: Department of Pharmaceutics, M. C. E. Society’s Allana College of Pharmacy, CIF-SPPU, Pune, between June 2018 and July 2021
 Methodology: In MWI different batches of SD were formulated by 32 factorial approach with time of exposure (X1) and power of radiation (X2) as variable quantity and dissolution rate as response (Y1). β-CD was used as hydrophilic carriers. Drug carrier magnitude relation of 1:1 resolve by phase solubility analysis and SD were assessed for drug content, percentage dissolution rate studies, FTIR, XRD, DSC and SEM analysis.
 Results: The FTIR, XRD, DSC and SEM studies exhibited no interaction between LPO and excipient. In Physical mixture (PM) it shows less intensity and disappearance of sharp peaks while in SD indicates the conversion of crystalline state of LPO to amorphous state that discovered the dissolution enhancing, so the SD prepared by MWI proved to be a promising approach to increasing the dissolving rate of BCS class II drug LPO.
 Conclusion: Hence, from the all analysis studies, it absolutely was evident that factorial batch F1 was the higher. F1 coded batch (LPO: β-CD within the magnitude relation of 1:1 with time of exposure (4 min) and power of radiation (300 Watt), shows 07 folds increase i.e. 84% compared with drug discharged inside 60 min to plane LPO and SD i.e. 12 % only and 84% respectively.

Medicated Supportive Braces: A Synergy of Treatments for Joint Pain Relief

Background and objectives: The present study unveils a simple but innovative combina-tion of existing treatments of three different domains with unique logical aspects. Joint pain is the major cause of disability, especially for older adults. Currently, two widely practiced treatment op-tions are combined to produce simultaneous treatments that overcome the drawbacks of individual treatment and improve patient compliance. Moreover, a third treatment option of cooling and coun-terirritant material (Menthol) for pain relief was also explored successfully as a substitute treatment. Method: In the present study, we formulated and optimized an adhesive topical patch of the model drug diclofenac sodium, a widely used medicine for pain relief and menthol, a cooling and counter-irritant substance to aid pain relief. Combinations of two polymers, PVP-K30 and PVA, selected by trial batches, were further optimized by applying a 3x2 full factorial design. Two factors, X1 (PVP-K30) and X2 (PVA), were optimized using three responses, R1 (Q2), R2 (Q4), and R3 (Q12). De-rived mathematical models for responses were validated using checkpoint batches. The final opti-mized batch was derived based on the desirability function. Factorial batches were also evaluated for relevant parameters. Results: Results obtained by checkpoint batches were in line with the experimental results with 5% relative error, revealing that the derived models were valid for the design. The final optimized batch obtained by the desirability function followed all set criteria. Medicated patch prepared by opti-mized formulation was incorporated into the knee brace using an in-house patch holder mechanism. Conclutions: Combined treatment offers better patient compliance for the patient and the healthcare provider, which can be extended to other pain-relieving supportive treatments like elbow braces, waist brace, back support belt, cervical brace, etc.

CENTRAL COMPOSITE DESIGN FOR FORMULATION AND OPTIMIZATION OF LONG-ACTING INJECTABLE (LAI) MICROSPHERES OF PALIPERIDONE PALMITATE

Objective: The aim of the present study was to optimize long-acting injectable (LAI) microspheres of Paliperidone palmitate (PP) for treatment of schizophrenia using face-centered central composite design (FC-CCD). Methods: In this study, poly lactic-co-glycolic acid (PLGA) based LAI microspheres of paliperidone palmitate (PP) were formulated by using FC-CCD. LAI microspheres were developed by using oil in water (O/W) emulsion solvent evaporation technique. On the basis of preliminary trials, FC-CCD was employed to check effect of independent variables such as drug polymer ratio (X1), homogenization speed (X2) and rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4), and drug release on day 60 (Y5) were considered as dependent variables and statistically evaluation performed by using design expert 12 software. Morphology of prepared microspheres was studied by using the scanning electron microscopy (SEM) technique, while particle size was analyzed by laser diffraction technique. In vitro drug release studies were performed using a controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study were performed to analyze any changes in crystal behavior or to detect any chemical bonding between ingredients. 13C NMR and 1H NMR techniques were used to analyze end-capping and monomer ratio in developed microspheres. Results: The factorial batches mean particle size was found to be 38 µm to 104 µm and drug loading were found between 27.2 % to 47.2%. Mathematical modelling of drug release kinetics revealed that near zero-order drug release of checkpoint formulations. Endcap analysis and molar ratio of formulated microspheres were found to be ester end cap and ~75:25, respectively. Morphologically all the prepared samples were found to be spherical in shape and smooth surface. FTIR data showed no significant interactions occurred between drug and excipients. The actual responses of checkpoint formulations were observed within 5% variation of predicted values. Conclusion: The prepared microspheres showed promising results of morphology, particle size, drug loading, entrapment efficiency, burst release and drug release on day 60. The successful predictive designs models were achieved from employed FC-CCD.

FORMULATION, EVALUATION AND OPTIMIZATION OF SUSTAINED-RELEASE DRUG DELIVERY SYSTEM OF CISAPRIDE TABLET

Objective: Cisapride is a novel prokinetic agent is best candidate for GERD. Cisapride 20 mg can be given thrice in a day given along with Proton pump inhibitor. By developing the sustain release formulation of Cisapride, the frequency of both drug can be reduce to once only to obtain good therapeutic response. Methods: Cisapride SR Tablets were prepared by direct compression technique with HPMC K4M and HPMC K100M polymers. Followed by various evaluation tests including in vitro disintegration and dissolution, the formulation was optimized by 32 full factorial designs with drug release kinetic analysis, compatibility studies (FTIR) and stability studies. Results: Results of Preformulation studies of the Cisapride indicate that it has poor flow property and compressibility property. To improve the flow and compressibility property, it was beneficial to use the directly compressible grade components in the formulation of tablet. Results of DSC study shown that there is no change in drug’s melting peak after the preparation of tablet. Hydrophilic matrix of HPMC K4M and HPMC K100M in combination sustained the Cisapride release effectively for more than 12h. The result indicates that the combination of HPMCK4M and HPMCK100M can be successfully, On the basis of the preliminary trials in the present study a32 full factorial design was employed to study the effect of independent variables, i.e. concentration of HPMCK4M(X1) and concentration of HPMCK100M(X2)on dependent variables like% drug release Q2, Q6 and Q10. Drug release is also dependent on the size of matrix tablets so, size and surface area was kept constant. Factorial batches F018, F019, F020, and F021 give the f2 value 75-100. Factorial batch F019 gives the highest f2 value 86.04 and also all the hour’s drug release was within the specified limits. Conclusion: The prepared formulation of Cisapride sustains release matrix tablet was stable and effective in treatment.

FORMULATION OPTIMIZATION AND EVALUATION OF TINIDAZOLE IN-SITU

The study deals with formulation optimization and evaluation of tinidazole gel by using sodium alginate as gelling agent calcium chloride, sodium citrate were used as cross linking agent. The polymeric solution of drug is in solution form before it administered to the body. But after administration when it comes in contact with acidic pH it’s converted into gel form and the drug tinidazole released from the dosage form constantly and slowly. The formulation is effective for the treatment of gastric ulcer because of Helicobacter pylori. 32 full factorial design were used for the optimization of the formulation 12 trial batches were prepared and 9 factorial design batches in which 2 factor 3 level factorial design were used for the optimization. The concentration of sodium alginate, were taken in 3 level low, medium, high and the prepared formulation were evaluated.

Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs.
 Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

STUDY OF THE FUNCTIONALITY OF A NOVEL SOLUTION BINDER OBTAINED FROM OCIMUM BASILICUM SEEDS: A MECHANISTIC APPROACH

Objective: The aim of the present study was to investigate the functionality of the hydrogel isolated from the seeds of Ocimum basilicum (Gel) as a novel solution binder.
 Methods: Paracetamol is known to possess poor manufacturability. Therefore it was selected as a model drug to study the efficiency of Gel as a solution binder. Paracetamol tablets were prepared at gradually increasing compression pressure from the granules prepared by using Gel of various viscosities as a solution binder. Compactibility parameter was calculated to assess the utility of Gel as a novel tablet binder. Optimization of the formulation was done by adopting factorial design as an appropriate DOE. Tablets of factorial batches were evaluated for disintegration time and crushing strength. The effect of viscosity of binder solution used to prepare granulation and compression pressure applied on granulation on the performance of the tablets was confirmed by analyzing the data using ANOVA.
 Results: The addition of binder solution to prepare granulation with the viscosity ≥ 19.33 centipoises was found to be suitable to attain desired degree of agglomeration. The crushing strength of the tablets was found to be increased with an increase in compression pressure and an increase in viscosity of binder solution.
 Conclusion: The compatibility parameter was observed to be increased as the viscosity of the binder solution added in the formulation was gradually increased. The Gel as a binder material was found to deform plastically at compression pressures 34.48 to 75.85 MPa. This confirmed its functionality as a solution binder in Paracetamol tablet preparation.

Formulation, Development and Evaluation of Chewable Bi-layered Tablets for Treating Gastro Esophageal Reflux Disease

The purpose of this research work was to formulate raft-forming chewable bilayer tablets of sodium alginate using a raft-forming agent along with gas-generating agents. Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralization capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as variables. Raft strength, acid neutralization capacity and drug release at 30 min were selected as responses.Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralization capacity and in vitro drug release of all factorial batches were found to be satisfactory. Prepared tablets were found to be pharmaceutically equivalent to the marketed product. It was concluded that raft-forming chewable bilayer tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux diseases.
 Keywords: Chewable bilayer tablet, Sodium alginate, Raft forming agent, Acid Neutralizing capacity

A STATISTICAL APPROACH TO DEVELOPMENT OF TASTE MASKED EFFERVESCENT TABLETS OF SILDENAFIL CITRATE CONTAINING KYRON T134

Objective: The aim of present work was to mask the bitter taste of sildenafil citrate by preparing drug resin complex (DRC) and develop sildenafil citrate 100 mg effervescent tablets.
 Methods: Sildenafil citrate and kyron T134 complexes were prepared at different conditions and evaluated for taste and drug loading. Optimized DRC was use to formulate the dispersible tablet by direct compression technique. A 32 full factorial design was use to study the effect of effervescent agent (X1) and croscarmellose sodium (X2) on dispersion time (Y1) and wetting time (Y2). Factorial batches were also evaluated for thickness, hardness, content uniformity, friability, in vitro drug release and stability studies. Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D plots were performing by using sigma plot 11.0. A Check point batch was design according to the results of desirability value and evaluated for all the parameter
 Results: FT-IR study confirm that sildenafil citrate and kyron T134 were compatible with each other. Among the various DRC batch B29 was found with less bitter and give a more drug loading. Checkpoint batch showed no significance difference between predicted value and actual value for dispersion time and wetting time and it was found stable during stability study.
 Conclusion: Sildenafil citrate bitter tast was masked by kyron T134 and full factorial design result was indicate that independent variables have significant effect on dependent variables

Statistical Design and Optimization of Sustained Release Formulations of Pravastatin.

The objective of the current study was to formulate a sustained release (SR) formulation for pravastatin. Pravastatin is a lipid lowering, biopharmaceutical classification class-III agent. SR tablets of pravastatin were prepared using variable amounts of hydroxy methyl propyl cellulose (HPMC) K4M and sodium carboxy methyl cellulose in various proportions by direct compression in a 32 factorial design. The amounts of the polymers HPMC K4M and sodium carboxy methyl cellulose required to obtain prolonged release of drug were chosen as independent variables, X1 and X2, respectively, whereas times taken for 10%, 50%, 75%, and 90% drug release were chosen as dependent variables. Nine formulations were developed and were checked using pharmacopoeial tests. The results showed that all the factorial batches were within the standard limits. The dissolution parameters of all formulations were subjected to kinetic fitting and various statistical parameters were determined. Polynomial equations were developed and verified for dependent variables. Formulation F5, containing 25 mg of HPMC K4M and 25 mg of sodium carboxy methyl cellulose, was the formulation most similar (similarity factor f2=89.559, difference factor f1=1.546) to the marketed product (Pravachol). The best formulation (F5) follows Higuchi's kinetics and non-Fickian diffusion zero order kinetics (n=1.083).

Formulation and Evaluation by Appling 32 (Three Squire) Factorial Design of Lercanidipine Hydrochloride Buccal Tablets with Mucoadhesive Polymers

Abstract: Aim: The aim of the present research work is to develop buccal tablets of Lercanidipine hydrochloride to reduce dosage frequency; obtain optimized and controlled therapy, better patient compliance. Materials and Methods: Lercanidipine HCL was obtained as a gift sample from Sun Pharma, Baroda, India. Other ingredients like Na-alginate, Carbopol 934 P, Micro Crystalline Cellulose, Mannitol, Magnesium stearate, Ethyl cellulose and Hydroxy Propyl Methyl CelluloseK4M were purchased from various sources. All other ingredients used were of analytical grade. Attempt was made by using mucoadhesive polymers HPMC K4 M, sodium alginate and carbopol 934 P in combination with Ethyl Cellulose as an impermeable backing layer. Results: Combination of polymer HPMC K4 M and sodium alginate release of drug was found in desired manner than other combinations. On the basis of the preliminary trials a 32 full factorial design was employed to study the effect of independent variables such as concentration of sodium alginate: HPMC K4M (X1) and type of filler (X2) on dependent variables. Factorial batches of F1 to F9 were formulated. HPMC K4M exhibited a much greater sustained effect on the release rate compared with sodium alginate. F4 shown the highest f2 value 70.46 and also all the h drug release was within the specified range. Based on the f2 value and targeted release profile the F4 batch was considered as optimized batch. Formulation F4 was subjected to an in vitro buccal permeation study. The results showed drug permeation of 99.04% in 12 h. The correlation between in vitro drug release rate and in vitro drug permeation across the chicken mucosa was found to be positive, with a correlation coefficient (R2) of 0.9921. Conclusion: From kinetic modelling of the dissolution profile of the optimized formulation, it was concluded that there is erosion-controlled release of Lercanidipine from the buccal adhesive drug delivery system. Key words: Lercanidipine hydrochloride, Buccal tablets, HPMC K4M, Buccal permeation study, Erosion controlled release.

OPTIMIZATION OF FORMULATION OF SOLID DISPERSION OF FUROSEMIDE BY FACTORIAL DESIGN

Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique.
 Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design.
 Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies.
 Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space.

FORMULATION AND EVALUATION OF RACECADOTRIL MUCOADHESIVE MICROSPHERES

Objective: To develop and evaluate the mucoadhesive microsphere using combinations of natural polymers chitosan and xanthan gum for sustained release.
 Methods: In the present work mucoadhesive microspheres were prepared by using natural polymers like chitosan and xanthan gum by using the emulsion chemical cross-linking method. Chemical cross-linking was done by using glutaraldehyde. The 22 factorial design was employed to show the effect of cross-linking agent and processing factor-like stirring and speed. Prepared microspheres were evaluated for their particle size, surface morphology, drug entrapment efficiency, in vitro drug release, swelling index, and mucoadhesive strength.
 Results: The size of microspheres of factorial batches were in the range of 26-46 µm. The swelling index was showed in the range of 1.51-1.66 percentage. The equation of multiple regression revealed that there was significant interaction among factors. The glutaraldehyde concentration had a positive effect on % entrapment efficiency, % cumulative drug release and % mucoadhesion. Stirring speed showed a negative impact on % entrapment efficiency, % cumulative drug release and % mucoadhesion. The interactive effect of glutaraldehyde concentration and the stirring speed was found to be positive for % entrapment efficiency and % cumulative drug release. In vitro drug release study of optimized formulation F2 show 96 % of drug release with 6 h indicating sustained release behavior with diffusion mechanism. The SEM image of the optimized batch was spherical with a porous surface.
 Conclusion: The results obtained in this research work indicated that a promising potential of chitosan and xanthan gum combination for the preparation of the mucoadhesive microsphere of Racecadotril.

DESIGN AND OPTIMIZATION OF PEDIATRIC CEFUROXIME AXETIL DISPERSIBLE TABLET CONTAINING ION-EXCHANGE RESIN

Objective: The aim of present work was to develop of pediatric cefuroxime axetil 125 mg dispersible tablets by using ion exchange resin as a taste masking agent and quality target product profile was defined based on the properties of the cefuroxime axetil.
 Methods: Initially, cefuroxime axetil and various resin complexes (DRC) were prepared with different conditions and evaluated for taste masking and drug loading. Optimized DRC was used to formulate the dispersible tablet. A 32 full factorial design was employed to study the effect of mannitol (X1) and microcrystalline cellulose PH-101 (X2) on drug release at 10 min and time taken to 80% drug release. In the present study, the following constraints were arbitrarily used for the selection of an optimized batch: Q10>65% and T80%<30 min. Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D plots were performed by using Sigmaplot 11.0. Checkpoint batch was prepared to validate the evolved model.
 Results: Among the various drug resins complex DRC-9 was found with less bitter taste which was containing kyron T-114 and among the all factorial batch F7 showed highest drug release at 10 min (Q10) and lowest time taken to 80% drug release (T80) hence batch F7 was selected as an optimized batch and it’s found to be stable in the stability evaluation.
 Conclusion: The results of full factorial design indicate mannitol and MCC PH-101 have a significant effect on drug release.

OPTIMIZATION OF AQUEOUS-BASED FILM COATING PROCESS PARAMETERS CONTAINING GLUCOSAMINE SULFATE POTASSIUM CHLORIDE

Objective: The aim of the present work was to prepare film coated tablet of glucosamine sulfate potassium chloride and study the effect of coating process parameters which implicate more significant effects on an aqueous-based film coating process of tablets.
 Methods: The different batches of uncoated tablets were prepared by wet granulation method. Aqueous film coating was carried out by using opadry®II white 85F18422. A 32 full factorial design was employed to study the effect of spray rate (X1) and inlet air temperature (X2) on coating uniformity, coating process efficiency and % loss on drying. The surface characteristics of the aqueous based film coated tablet were studied using a SEM. Check point batch was prepared to validate the evolved model.
 Results: Preliminary trials indicated that individually process parameters affected the quality of coated tablets. Hence, studied the combined effect of these factors on the coating process required and 32 full factorial design was applied. In this study, it was seen that spray rate and inlet air temperature had a major effect on tablet coating process. It was observed from factorial batch that maximum drug release was found in batch F5.
 Conclusion: The results of full factorial design indicate both parameters spray rate (X1) and inlet air temperature (X2) have significant effect on coating process and batch F5 is stable for 3 mo at accelerated condition.