Independent Formulation Variables Research Articles

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

Thin film hydration versus modified spraying technique to fabricate intranasal spanlastic nanovesicles for rasagiline mesylate brain delivery: Characterization, statistical optimization, and in vivo pharmacokinetic evaluation

Rasagiline mesylate (RM) is a monoamine oxidase inhibitor that is commonly used to alleviate the symptoms of Parkinson’s disease. However, it suffers from low oral bioavailability due to its extensive hepatic metabolism in addition to its hydrophilic nature which limits its ability to pass through the blood–brain barrier (BBB) and reach the central nervous system where it exerts its pharmacological effect. Thus, this study aims to form RM-loaded spanlastic vesicles for intranasal (IN) administration to overcome its hepatic metabolism and permit its direct delivery to the brain. RM-loaded spanlastics were prepared using thin film hydration (TFH) and modified spraying technique (MST). A 23 factorial design was constructed to study and optimize the effects of the independent formulation variables, namely, Span type, Span: Brij 35 ratio, and sonication time on the vesicles᾽ characteristics in each preparation technique. The optimized system prepared using MST (MST 2) has shown higher desirability factor with smaller PS and higher EE%; thus, it was selected for further in vivo evaluation where it revealed that the extent of RM distribution from the intranasally administered spanlastics to the brain was comparable to that of the IV drug solution with significantly high brain-targeting efficiency (458.47%). These results suggest that the IN administration of the optimized RM-loaded spanlastics could be a promising, non-invasive alternative for the efficient delivery of RM to brain tissues to exert its pharmacological activities without being dissipated to other body organs which subsequently may result in higher pharmacological efficiency and better safety profile.Graphical

Design, fabrication, optimization and characterization of memantine-loaded biodegradable PLGA nanoscaffolds for treatment of Alzheimer’s disease

This study aimed to design and develop nanoscaffolds for the controlled release of memantine by non-solvent-induced phase separation (N-TIPS) method. The development and optimization of nanoscaffolds was performed by Box–Behnken Design in which two independent formulation variables and one independent process variable: poly(lactic-co-glycolic acid) (PLGA) (X 1), Pluronics F-127 (X 2), and rotation speed (X 3) were used. The design provided 15 formulation designs which were prepared to determine the response: percentage porosity (Y 1) and drug loading (Y 2). Polynomial equations were generated and analyzed statistically to establish a relationship between independent and dependent variables and develop an optimal formulation with maximized porosity (%) and drug loading (%). The optimized formulation batch was prepared using 19.18% w/v PLGA, 4.98% w/v Pluronics at 500 rpm rotation speed and exhibited drug loading of 11.66% and porosity of 82.62%. Further, correlation between the independent and dependent variables were established and statistically analyzed by using model generated mathematical regression equations, ANOVA, residual plots, interaction plot, main effect plot, contour plot and response surface designs. The analysis of model showed the significant individual effect of PLGA and significant interactive effect of Pluronics F-127 and rotation speed on drug loading and porosity. Further, its physicochemical characterization, and in-vitro (drug release kinetics, and PAMPA study), ex-vivo (enzyme inhibition assay and pro-inflammatory cytokines study) and in-vivo (neurobehavioral and histological study) studies were performed to evaluate the potential of memantine-loaded nanoscaffolds in the treatment of Alzheimer’s disease (AD).

Formulation Development, Evaluation and Statistical Optimization of the Release Rate of Oral Sustained Release Matrix Tablet of Aceclofena

Aim: This work aimed to develop a sustained released hydrophilic matrix tablet of Aceclofenac for better therapeutic action. &#x0D; Background: Conventional dosage form didn't provide the desired level of drug release. Even many-marketed sustained-release tablets didn't always meet the satisfactory level of drug release. It was a challenging job for pharmaceutical scientists to develop a well-sustained release formulation. Keeping this perspective in mind a robust sustained release formulation was designed, developed and optimized with nontoxic, inert viscoelastic, semisynthetic polymers which will be accepted worldwide.&#x0D; Objective: The objective of this research was to develop an Aceclofenac sustained released matrix tablet, which will deliver the desired level of drug release.&#x0D; Method: Aceclofenac sustained released tablet was prepared with Methocel K-100M Premium (Hydroxypropyl Methylcellulose) and Unigel 270 (Pregelatinized starch). These two excipients were selected as independent formulation variables with three separate levels (high, intermediate and low). Nine batches of hydrophilic matrix tablets of Aceclofenac were prepared according to the 32 Factorial Design with an average weight of 365 mg/tablet. Each prepared batch of tablets was then evaluated for drug content, physical parameters and drug release. Mathematical models were then generated using Analysis of Variance employing Design-Expert Software version 8.0.7.1 for % cumulative release at T1 hr, T4 hr and T7 hr. FTIR spectroscopy was carried out to evaluate drug-excipients interaction after formulation.&#x0D; Results: Design-Expert Software after analyzing the release data of prepared 9 batches provides an optimized composition of formulation. The optimized batch showed desirable results for cumulative % release (CPR)T1hr, CPR T4hr and CPR T7hr are 35.61, 52.16 and 61.98 respectively. &#x0D; Conclusion: Application of statistical experimental design, the physicochemical studies and the in vitro-release study, the mathematically predicted formulation and its manufacturing and validation of aceclofenac sustained-release tablets showed great advancement from the trial-and-error method of development of sustained-release drug delivery systems.

APPLICATION OF LIQUISOLID SYSTEMS IN MODIFYING DRUG RELEASE OF GLICLAZIDE

Liquisolid technique is an emerging technology of formulation development. In the present work, a modified-release formulation of gliclazide was developed by using the liquisolid technique. Gliclazide was dispersed in a nonvolatile solvents system of Tween 80 and propylene glycol, followed by adsorbing the liquid medication on carrier material MCC pH 102. Drug release rate controlling polymer HPMC was wet granulated with binder solution along with diluent. The two blends of API liquisolid and polymer mixture were blended uniformly with extra granular excipients to manufacture gliclazide modified release tablets 30 mg. Characterization of gliclazide liquisolid tablets was done using analytical techniques, i.e., FTIR and XRD. The optimization of the formulation was done by using mixture design where the amount of propylene glycol, Tween 80, DCP (anhydrous), HPMC K4M and HPMC K100 LVCR were considered to be the independent formulation variables. The dissolution and hardness were considered as dependent variables. The formulations were evaluated for dissolution, assay, hardness, thickness and other vital properties. The liquisolid formulation showed a zero-order release pattern and matched with the innovator (Diamicron MR 30 mg). The modified release tablets showed good stability at 40 °C / 75% RH for three months.

Development and Rheological Evaluation of DEET (N,N-DiethyL-3-Methylbenzamide) Microparticles Loaded Hydrogel For Topical Application

N,N-Diethyl-3-methylbenzamide (DEET) is a broad-spectrum insect repellent that can easily permeate through the skin and can cause undesirable effects, especially in children and pregnant women. The objective of this research was to formulate and evaluate DEET-encapsulated microparticles containing a hydrogel designed to reduce skin permeation and prolong drug release. The formulation design was based on the independent formulation variables of the concentration of chitosan and sodium tripolyphosphate using a simple factorial design experiment. DEET-loaded microparticles were developed and incorporated into a hydrogel. The size of the microparticles was analyzed using the Zetasizer Nano® particle size analyzer, and the surface morphology, using field emission scanning electron microscopy. Drug release from the microparticles was determined by the dialysis bag method. A rheological evaluation of the formulated gel was performed using a Thermo Haake Rheometer. The in vitro permeation of the formulation was performed using a synthetic Strat-M® membrane. The size of the microparticles ranged from 0.45 to 8.3 μm, and the encapsulation efficiencies were >50% for all the formulations. The drug-release curves showed no initial burst release from the microparticle formulation. Instead, a slow and controlled drug release was observed over 24 hours that followed Higuchi kinetics. The cumulative amount of DEET permeated (over 24 h) from the DEET solution (control), and the formulation was 211.6±19.5 μg/cm2 and 4.07±0.08 μg/cm2, respectively. A significantly low DEET permeation from the microparticle formulations indicated minimal absorption of the drug into the body and thus, reduced systemic toxicity. Thixotropic evaluation of the hydrogel formulation demonstrated a hysteresis loop that fitted closely to the Herschel-Bulkley rheological model, ensuring an effortless application and prolonged retention on the skin. Hence, it can be concluded that the developed formulation is an effective delivery approach for controlled insect repellent activity with reduced skin absorption.

Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique.

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.

Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing.

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol–gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (−23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300–500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.

Enhancing the Low Oral Bioavailability of Sulpiride via Fast Orally Disintegrating Tablets: Formulation, Optimization and In Vivo Characterization.

Sulpiride (SUL) is a dopamine D2-receptor antagonist used for management of GIT disturbance and it has anti-psychotic activities based on the administered dose. SUL undergoes P-glycoprotein efflux, which lead to poor bioavailability and erratic absorption. Therefore, the objective of this research was an attempt to enhance the oral bioavailability of SUL via formulation of fast disintegrating tablets (SUL-FDTs) with a rapid onset of action. A 32 full-factorial design was performed for optimization of SUL-FDTs using desirability function. The concentration of superdisintegrant (X1) and Prosolv® (X2) were selected as independent formulation variables for the preparation and optimization of SUL-FDTs using direct compression technique. The prepared SUL-FDTs were investigated regarding their mechanical strength, disintegration time, drug release and in vivo pharmacokinetic analysis in rabbits. The optimized formulation has hardness of 4.58 ± 0.52 KP, friability of 0.73 ± 0.158%, disintegration time of 37.5 ± 1.87 s and drug release of 100.51 ± 1.34% after 30 min. In addition, the optimized SUL-FDTs showed a significant (p < 0.01) increase in Cmax and AUC(0–∞) and a relative bioavailability of about 9.3 fold compared to the commercial product. It could be concluded that SUL-FDTs are a promising formulation for enhancing the oral bioavailability of SUL concomitant with a fast action.

Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach.

This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy. The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide. Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 23 full factorial design. The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile. The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41± 2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9. This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.

Defining design space for optimization of escitalopram ultra-fast melting tablet using suspension spray-coating technique: In-vitro and in-vivo evaluation

In the pharmaceutical industry, the systematic optimization of formulation using Quality by Design (QbD) approach is economic, highly precise and ensures product quality. The current endeavor was aimed to prepare escitalopram ultra-fast melting tablets (UFMTs) based on QbD approach using suspension spray-coating technique. The (32) full factorial design was applied to obtain the optimal formulation in terms of; mannitol level (X1) and partially pre-gelatinized starch level (PPGS; X2) as independent formulation variables. The D-mannitol in certain formulations was spray-coated with a suspension of PPGS and granulated with distilled water (without PPGS) in other formulations using a fluid-bed granulator, producing granules compressed into tablets. The prepared tablets were tested for their mechanical strength, in-vitro and in-vivo disintegration, drug dissolution and in-vivo pharmacokinetic analysis using New Zealand rabbits. Results showed that the prepared tablets were tolerated with the USP criteria. Besides, ANOVA analysis demonstrated that X1 and X2 had a significant effect (P ≤ 0.05) on the dependent responses. Further, the developed tablets showed a good in-vitro/in-vivo correlation (R2 = 0.9953) in the disintegration time. Moreover, analysis of pharmacokinetic parameters suggested that optimized escitalopram UFMTs might have pharmaceutical bioequivalence to the marketed product. Finally, QbD considered an efficient paradigm for product optimization.

Natural astaxanthin encapsulation: Use of response surface methodology for the design of alginate beads

Nowadays, consumers are more conscious about healthier products consumption benefits. Astaxanthin obtained from the microalgae Haematococcus pluvialis represents a natural ingredient for the nutraceutical and functional food industries. It is claimed that astaxanthin has much stronger antioxidant activity than vitamin E and β-carotene, providing different health benefits. However, the unstable structure of the molecule limits its application in functional foods development. Therefore, the present study evaluates the effect of five independent formulation and process variables for natural astaxanthin oleoresin encapsulation using an external ionic gelation technique. Response surface methodology can be used for studying the effect of several factors at different levels and their influences on each other, which overcomes the shortcoming of the traditional orthogonal method. The results showed that alginate and CaCl2 concentrations have a significant effect on particles size obtained, while alginate/oleoresin ratio and surfactant concentration greatly influence the astaxanthin oleoresin release rate. In vitro studies under simulated intestinal conditions showed that astaxanthin oleoresin release process can be described by Hopfenberg model. Three mathematical models were obtained for predicting particle size, astaxanthin release rate and encapsulation yield under different process conditions, providing a platform for microencapsulation technology optimization for healthy food design.

Statistical moments in modelling of swelling, erosion and drug release of hydrophilic matrix-tablets

Statistical moments were evaluated as suitable parameters for describing swelling and erosion processes (along with drug release) in hydrophilic controlled release matrix tablets. The effect of four independent formulation variables, corresponding to the quantity of four polymeric matrix excipients (namely polyethylene glycol, povidone, and two grades of hydroxyl-propylmethyl cellulose) on statistical moments describing swelling (mean swelling time, MST), erosion (mean erosion time, MET) and drug-release (mean dissolution time, MDT) was evaluated with the aid of multi-linear regression (MLR) and artificial neural networks (ANNs) based on a central composite experimental design. Results were compared to conventional model fitting, where the rate of water uptake during swelling (a), the maximum % water uptake (Smax), the time at which Smax is achieved (tmax), the constant of apparent matrix-tablet erosion rate (ke) and the release exponent (n) from Korsmeyer-Peppas drug-release equation were used as model parameters. Fitting to an external validation test set revealed superior prediction efficacy for statistical moments compared to conventional model fitting, while the combination of statistical moments with ANNs presented the most efficient approach (R2 and RMSEp values of 0.922, 0.833, 0.987 and 0.443, 0.691, 0.173 for MST, MET, and MDT, respectively).

Topical Analgesic Nanolipid Vesicles Formulation of Capsaicinoids Extract of Bhut Jolokia (Capsicum chinense Jacq): Pharmacodynamic Evaluation in Rat Models and Acceptability studies in Human Volunteers

Capsicum fruit is used for treating skeletomuscular disorders as a counterirritant analgesic around the globe. But its concentration-dependent irritation and concomitant withdrawal of therapy by the patients hampers its therapeutic usefulness. In the present study, a novel nanolipid approach based on elastic phospholipid vesicles was employed to encapsulate a semipurified extract of Bhut Jolokia for topical drug delivery application. The working hypothesis was that encapsulation of irritant extract into nanolipid vesicles may prevent the initial rejection of formulation and the elastic vesicles may facilitate deeper skin penetration over a shorter time period. Surface response methodology was adopted to study the effect of selected independent formulation variables on dependent variables like vesicle size and entrapment efficacy. The prepared formulations were characterized for various physicochemical parameters. The efficacy of the newly developed nonolipid vesicle formulation loaded with semipurified extract of Bhut Jolokia was tested on carrageenan and formaldehyde-induced inflammation as well as Freund's adjuvant-induced arthritis model. The novel formulations were tested on human volunteers in a Phase I clinical trial and were found to be acceptable. The study indicates that this strategy holds immense potential for topical delivery of the bioactive from Bhut Jolokia and can pave the way for its clinical applications.

Design and Optimization of Rivaroxaban Lipid Solid Dispersion for Dissolution Enhancement using Statistical Experimental Design

Aim: The purpose of the present study was to understand the effect of formulation variables of lipid solid dispersion on the dissolution of a model drug, rivaroxaban. Method: A three-factor, three-level Box–Behnken design was used to explore the main and interaction effect of several independent formulation variables including the amount of Gelucire 48/16 (X1), Compitrol HD5 ATO (X2), and Labrasol (X3). Particle size (Y1) and dissolution percentage of rivaroxaban (Y2) were the dependent variables. Statistical Analysis: A mathematical relationship was obtained to explain the effect of all factors and their colinearities on the dissolution of rivaroxaban. Results: A formulation optimization was then performed to maximize dissolution percentage of rivaroxaban (Y2). The optimized formulation was predicted to dissolution 62.4% of rivaroxaban at 5 min, when X1, X2, and X3 values were 20.0, 30.0, and 2.0 mg, respectively. Conclusion: In conclusion, the Box–Behnken experimental design allowed us to understand the effect of formulation variables on the dissolution of rivaroxaban from lipid solid dispersion, and optimize the formulation to obtain drug dissolution.

Gastroretentive extended release of metformin from methacrylamide-g-gellan and tamarind seed gum composite matrix

Formulation of a gastroretentive extended release tablet of metformin based on polymethacrylamide-g-gellan (Pmaa-g-GG)-tamarind seed gum (TSG) composite matrix is the main purpose of this study. Tablets were prepared employing wet granulation method taking amount of Pmaa-g-GG, TSG and NaHCO3 (SBC, buoyancy contributor) as independent formulation variables. The tablets were then evaluated for in vitro drug release, buoyancy, ex vivo mucoadhesion, swelling and surface morphology. Compatibility between drug and excipients was checked by DSC, FTIR and XRD analysis. Buoyancy-lag-time, mucoadhesive strength, % drug release and release-rate constant were statistically analyzed using Design-Expert software (version 9.0.4.1) and the formulation was then numerically optimized to obtain USP-reference release profile. The optimized formulation showed excellent buoyancy over a 10h period with buoyancy lag time of 2.76min, significant mucoadhesion and drug release over a period of 10h with f2=71.58. Kinetic modeling unveiled anomalous non-Fickian transport based drug release mechanism.

Optimization of a Novel Oral Colon Delivery System of Indomethacin Using Full Factorial Design

Purpose: To develop and optimize indomethacin (IDM) matrix tablets for specific colon drug delivery.Methods: Indomethacin matrix tablets containing hydrogenated castor oil (HCO), and pectin (PEC) were prepared by hot fusion method. A 32 full factorial design was used to investigate the combined effect of two independent formulation variables, X1 and X2, namely, the amount of HCO and PEC, respectively. Their effect on IDM release from the matrix tablets in acidic medium (0.1 N HCl) and phosphate buffer (pH 6.8), were analyzed and optimized. A contour plot was also applied to graphically represent the effect of the independent variables on drug release in pH 6.8 medium at 2 h (Y1) and 24 h (Y2), and the time required for 25 % drug release (Y3) as dependent variables.Results: The optimized IDM matrix tablets showed almost total retardation of drug release in acidic medium and prolonged sustained release in pH 6.8 medium over 24 h. The correlation coefficient (R2) value for Y1, Y2 and Y3 were 0.99850, 0.9980 and 0.9970, respectively, indicating good correlation between dependent and independent variables. Differences between the coefficients for Y1, Y2 and Y3 were significant (p &lt; 0.05), and hence contributed significantly to the prediction of the independent variables.Conclusion: The findings indicate that successful design, development, and optimization of IDM matrix tablets for colon delivery has been achieved.Keywords: Indomethacin, Hydrogenated castor oil, Pectin, Factorial design, Matrix tablets, Colondelivery system

Dose calculation, design and development of nateglinide matrix tablets using quality by design approach and its pharmacokinetic evaluation in animal model

The present work deals with design of zero order sustained release nateglinide matrix tablets by application of statistical design using response surface methodology as a tool. Central composite design was used to investigate the effect of two independent formulation variables (at three levels) such as Kollidon SR (X1), PVP K 30 (X2) on dependent variables viz. time required to release 30 % (T30, Y1), percentage drug released at 6th hour (DR6, Y2) and time required to release 90 % (T90, Y3) of drug. Wet granulation technique was employed for tablets preparation. The result showed that release pattern of the optimized formulation was almost equal to the statistically predicted values. There was no chemical interaction observed between drug and polymer based up on FTIR and DSC results. In vitro release studies were performed in 0.1 N HCl containing 0.5 % SLS for first 2 h followed by pH 6.8 phosphate buffer containing 0.5 % SLS. Stability studies were performed to statistically optimized formulation. The release pattern from statistically optimized formulation was followed zero order kinetics with non-Fickian process as drug release mechanism. Pharmacokinetic studies were performed to optimized formulation in comparison with nateglinide suspension in rabbit as animal model. The results of in vivo studies revealed the % relative bioavailability of statistically optimized formulation was found to be 68.87 %.

Formulation optimization of mouth dissolving tablets of Meloxicam using mixed hydrotropic solublization technique

The objective of the present study was to develop mouth dissolving tablets of meloxicam in order to achieve rapid release in saliva which may result in enhanced absorption and thereby improved bioavailability. Six batches of mixed hydrotropic solid dispersions and physical mixtures were prepared using different ratios (1:2, 1:4 and 1:6) of hydrotropic blends (urea, Nicotinamide &amp; sodium citrate). The best batch was selected to prepare mouth dissolving tablets comprising solid dispersion of Meloxicam in six preliminary batches using croscarmellose sodium &amp; crospovidone as superdisintegrants and camphor as subliming agent in different ratios along with other excipients. Secondary batches were prepared based on 32 factorial design with amount of superdisintegrant (crospovidone) and camphor (subliming agent) as two independent formulation variables. Two dependent response variables considered were disintegration time and percentage friability. All the batches of mouth dissolving tablets were evaluated for pre-compre sion parameters and post-compression parametes. The results of accelerated stability studies revealed no physical and chemical changes in the tablets during three months.

Formulation of Rosuvastatin-Loaded Self-Nanoemulsifying Drug Delivery System Using Box-Behnken Design

The objectives of present study were to understand the effect of formulation variables of self-nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin (RSV). Box-Behnken design in conjunction with desirability function was used to evaluate the main effect, interaction effect and quadratic effect of independent formulation variables that included amounts of Acconon 200 E6, Cremophor RH40, and Lipoxol 300. For a better understanding of the selected variables for the optimal performance of RSV SNEDDS, the models were presented as three-dimensional response surface graphs. A fresh batch of optimized formulations and were prepared with optimized levels of the independent variables to yield dependent variables (Y1–Y6) values that were remarkably close to the predicted values. Drug excipient compatibility studies using the Fourier transform infrared spectroscopy, differential scanning calorimeter and x-ray diffraction indicated the absence of any incompatibility between RSV and selected excipients. The transmission electron microscopy of selected optimized SNEDDS of RSV showed the spherical shape of globules with no signs of coalescence and precipitation of RSV. The study demonstrates the use of Box-Behnken design for the preparation of RSV SNEDDS. The desirable goals can be obtained by systematic formulation approach in minimum possible time.