Vaishali Thakkar

Goodness-of-Fit Model-Dependent Approach for Release Kinetics of Levofloxacin Hemihydrates Floating Tablet

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.

Effect of Solvent on Crystal Habit and Dissolution Behavior of Tolbutamide by Initial Solvent Screening

By an initial solvent screening of 18 solvents, 14 pure good solvents were selected for the crystallization of tolbutamide. Solid gener ation by the solvent-change method was carried out using the pure good solvents. Crystals were generated in only 10 of the 14 solvents. Different crystal forms of tolbutamide were obtained. Crystals were subjected to evaluation tests such as differential scanning calorimetry, optical microscopy, and in vitro dissolution. All crystals were determined as isomorphic by differential scanning calorimetry. Dissolution rate was influenced by crystal form. Thus, the choice of suitable crystal habit and proper selection of solvent is important in manufacturing the drug tolbutamide.

Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept

Abstract Context: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability. Objective: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation. Materials and methods: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug. Results and discussion: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption. Conclusion: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.

Development and characterisation of thermo reversible mucoadhesive moxifloxacin hydrochloride in situ ophthalmic gel

A sustain release thermo reversible in situ gel of Moxifloxacin Hydrochloride using mucoadhesive polymer was prepared. Mucoadhesive polymer was used to obtain an ophthalmic delivery system with improved mechanical and mucoadhesive properties that will provide prolong retention time for treatment of ocular diseases. Developed formulations were evaluated for drug-excipient compatibility study, pH, Clarity, Gelation temperature study, Mucoadhesion properties and in-vitro release studies. Drug-excipient compatibility study was performed by FTIR technique. The individual IR spectra of the pure drug and polymers as well as the combination spectra of the drug and polymer were taken, which indicate no interaction between Moxifloxacin and polymers when compared with infrared spectrum of pure drug as all functional group frequencies were present. The values of other parameters obtained were in acceptable range. In vitro release tests revealed that 98% drug was released from the in situ gel containing 0.5% and 1.00% HPMC in 12 hr. provides prolonged release.

Formulation and evaluation of clotrimazole transdermal spray

Abstract 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 <85° and uniform spray pattern. The formulation containing PG showed higher drug release than PEG 400. The inclusion of eutectic mixture consisting of camphor and menthol (1:1) showed improved drug transport through the rat skin and larger mean zone of inhibition indicating the improved antifungal efficacy. Conclusion: The TS of CTZ can be an innovative and promising approach for the topical administration in the fungal diseases.

Effects of spray drying conditions on the physicochemical properties of the Tramadol-Hcl microparticles containing Eudragit® RS and RL

The preparation of Tramadol-HCL spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug–polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain tramadol spray-dried microspheres using the Eudragit® RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. The effects of matrix composition on microparticle properties were characterized by Laser Light scattering, differential scanning calorimetry (DSC), X-ray diffraction study, FT-infrared and UV-visible spectroscopy. The spray-dried microparticles were evaluated in terms of shape (SEM), size distribution (Laser light scattering method), production yield, drug content, initial drug loding and encapsulation efficiency. The results of X-ray diffraction and thermal analysis reveals the conversion of crystalline drug to amorphous. FTIR analysis confirmed the absence of any drug polymer interaction. The results indicated that the entrapment efficiency (EE), and product yield were depended on polymeric composition and polymeric ratios of the microspheres prepared. Tramadol microspheres based on Eudragit® blend can be prepared by spray-drying and the nebulization parameters do not influence significantly on particle properties.

Optimization of aceclofenac solid dispersion using Box-Behnken design: in-vitro and in-vivo evaluation.

The study investigates the combined influence of three independent variables in preparation of aceclofenac ternary solid dispersion (SD) by kneading method. A 3-factor, 3-level Box-Behnken design was used. Independent variables selected were microcrystalline cellulose (Avicel 200 = X1), hydroxypropyl methylcellulose-5 cps (HPMC E-5 = X2), and ratio of drug to polymer mixture (X3). Fifteen batches were prepared and evaluated for angle of repose and percentage drug release at 5 minutes (Q5). The transformed values of variables were subjected to multiple regression analysis to establish a second-order polynomial equation. Contour plots were constructed to evaluate the effects of X1, X2 and X3 on Q5 and angle of repose. Model was validated for accurate prediction of Q5 and angle of repose (AR) by performing checkpoint analysis. The computer optimization process and contour plots predict the levels of independent variables as X1= +0.5, X2 = -1 and X3 = +0.35 for maximized response of Q5 with better flow property. The stability study during 6 months confirms that aceclofenac exhibits high stability in solid dispersion. In vivo studies indicate that optimized ternary solid dispersion provides rapid pharmacological responses in mice and rats compared to marketed formulation.

Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns

Introduction: The aim of burn management and therapy is fast healing and epithelisation to prevent infection. The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD) and Aloe vera for topical treatment of infected burns. Methods: Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase Glyceryl Monooleate (GMO) and Poloxamer 407. The optimum formulae were incorporated in an aloe vera gel containing carbopol 934, to form cubosomal hydrogels (cubogels). The cubogels were characterized by in vitro release of SSD, rheological properties, pH, bioadhesion, Transmission Electron Microscopy and in-vivo Wound Healing Study. Results: The results show that the different concentration of GMO had significant effect on particle size, % EE and in vitro drug release. From the in-vitro drug release pattern and similarity factor (f2), it was concluded that batch CG3 (15% GMO and 1% P407) exhibited complete and controlled drug release within 12 hour (i.e. 98.25%), better bio adhesion and superior burn healing as compared to the marketed product. Conclusion: The in vivo burns healing study in rats revealed that the prepared optimized cubogel containing SSD and aloe vera has superior burns healing rate than cubogel with only SSD and marketed preparation so, it may be successfully used in the treatment of deep second degree burn.

Cleaning Validation: Quantitative Estimation of Atorvastatin in Production Area

Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. UV spectrophotometric and total organic carbon–solid sample module (TOC-SSM) method was developed and validated for the verification and determination of atorvastatin residues in the production area and to confirm the efficiency of the cleaning procedure as per ICH guideline. Atorvastatin was selected on the basis of a worst-case rating approach. It exhibited good linearity in the range of 5 to 25 μg/mL for UV spectrophotometric and 7300 to 83800 μg for the TOC-SSM method. The limit of detection was 0.419 μg/mL and 4.19 μg in the UV spectrophotometric and TOC-SSM methods, respectively. The limit of quantitation was 1.267 μg/mL and 12.69 μg in UV spectrophotometric and TOC-SSM methods, respectively. Percentage recovery from spiked stainless steel plates was found to be 95.37% and 92.82% in UV spectrophotometric and TOC-SSM methods, respectively. The calculated limit of acceptance per swab for atorvastatin (35.65 μg/swab) was not exceeded during three consecutive batches of production after cleaning procedure. Both proposed methods are suitable for quantitative determination of atorvastatin on manufacturing equipment surfaces well below the limit of contamination. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue with precision and accuracy. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative to confirm the efficiency of the cleaning procedure in pharmaceutical industries. LAY ABSTRACT: Carefully designed cleaning validation and its evaluation can ensure that residues of active pharmaceutical ingredient will not carry over and cross-contaminate the subsequent product. Atorvastatin was identified as a potential candidate among existing drug substances in production areas based on a worst-case rating approach. Atorvastatin residues were detected and quantified below acceptance limits after cleaning of production equipment using two proposed methods, namely, the UV spectrophotometric and total organic carbon–solid sample module (TOC-SSM) methods. The ease of sample preparation permits fast and efficient application of the proposed methods in quantitation of atorvastatin residue in production equipment area to confirm the efficiency of the cleaning procedure in pharmaceutical industries. Above all, the methodology is of low cost, and is a simple and less time-consuming alternative for cleaning validation.

Development of Biodegradable injectable in situ forming implants for sustained release of Lornoxicam

OBJECTIVE The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. METHODS Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. RESULTS The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. CONCLUSION Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.