Mukesh C. Gohel

Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique

The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

Microneedles: an emerging transdermal drug delivery system

Objectives  One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area.

Preparation and Assessment of Novel Coprocessed Superdisintegrant Consisting of Crospovidone and Sodium Starch Glycolate: A Technical Note

Summary and ConclusionCoprocessed superdisintegrant consisting of crospovidone and SSG exhibited good flow and compression characteristics. Cefixime trihydrate and ibuprofen tablets containing coprocessed superdisintegrant exhibited quick disintegration and improved drug dissolution.

Novel mathematical method for quantitative expression of deviation from the higuchi model.

A simple mathematical method to express the deviation in release profile of a test product following Higuchis kinetics from an ideal Higuchi release profile was developed. The method is based on calculation of area under the curve (AUC) by using the trapezoidal rule. The precision of prediction depends on the number of data points. The method is exemplified for 2 dosage forms (tablets of diltiazem HCl and microspheres of diclofenac sodium) that are designed to release the drug over a 12-hour period. The method can be adopted for the formulations where drug release is incomplete (<100%) or complete (100%) at last sampling time. To describe the kinetics of drug release from the test formulation, zero-order, first-order, Higuchis. Hixson-Crowells, and Weibulls models were used. The criterion for selecting the most appropriate model was based on the goodness-of-fit test. The release kinetics of the tablets and microspheres were explained by the Higuchi model. The release profiles of the test batches were slightly below the ideal Higuchi release profile. For the test products, observed percentage deviation from an ideal Higuchi profile is less than 16% for tablets and less than 11% for microspheres. The proposed method can be extended to the modified release formulations that are designed to release a drug over 6, 18, or 24 hours. If the data points are not evenly separated, the ideal drug release profile and AUC are calculated according to the specific sampling time. The proposed method may be used for comparing formulated products during the research and development stage, for quality control of the products, or for promoting products by comparing performance of the test product with that of the innovators product.

Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: a technical note.

Summary and ConclusionThe coprocessed superdisintegrant proved to be superior to the physical blend in terms of flow due to size enlargement. Furthermore, the coprocessed superdisintegrant displayed superiority in terms of crushing strength, disintegration time, and drug dissolution. The advantages of the proposed method are easy adaptability in industry and the possibility of bypassing the existing patents in the ereas of quick disintegration and dissolution.

A More Relevant Dissolution Method for Evaluation of Floating Drug Delivery System

Introduction A modified release drug delivery system with prolonged residence time in the stomach is of particular interest for drugs: (a) that are locally acting in the stomach, (b) that have an absorption window in the stomach or in the upper part of small intestine, (c) that are unstable in the intestinal or colonic environments, or (d) have low solubility at high pH values. Systems that prolong the gastric residence time can also be used as sustained release devices with a reduced frequency of administration and therefore, can improve patient compliance (1). Approaches to increase gastric residence time include: (a) bioadhesive delivery systems that adhere to mucosal surfaces, (b) delivery systems that increase in size to retard passage through the pylorus, and (c) density-controlled delivery systems, that either float or sink in gastric fluids (2-6). In vitro dissolution testing is generally carried out for quality control purposes and to establish an in vivo in vitro correlation. Traditional in vitro dissolution methods have been shown to be poor predictors of in vivo performance for floating dosage forms (7).The currently used in vitro dissolution methods do not mimic the conditions present in the stomach. Researchers around the world have tried different methods for studying in vitro dissolution for floating drug delivery systems (8,9). However, each of the methods has some limitations. Hence, a modified in-vitro dissolution method was evaluated.

Processing of Nimesulide-PEG 400-PG-PVP Solid Dispersions: Preparation, Characterization, and In Vitro Dissolution

Abstract The objective of this investigation was to study the influence of dissolution enhancers such as polyethylene glycol 400, propylene glycol, polyvinylpyrrolidone K30, sodium lauryl sulfate, and Tween 80 on in vitro dissolution of a model active pharmaceutical material—nimesulide. Preliminary studies were conducted using a physical blend of nimesulide, and the adjuvants and solid dispersions were prepared using solvent evaporation and cogrinding methods. Aqueous solution of adjuvants was first triturated with nimesulide, followed by mixing with lactose and microcrystalline cellulose, and finally water was evaporated under vacuum in a cogrinding method. A 33 factorial design was adopted in a cogrinding method using the concentration of polyethylene glycol 400, propylene glycol, and polyvinylpyrrolidone K30 as independent variables. Tween 80 and sodium lauryl sulfate were added in all the batches. Full and reduced models were evolved for different dependent variables. The reduced models were validated using two checkpoints. Angle of repose <35°, percentage of drug released in 30 min (Q30)>40%, 45 min (Q45)>50%, and 120 min (Q120)>60% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependent variables. Polyvinylpyrrolidone was found to be more effective in increasing the drug dissolution, compared with polyethylene glycol 400 and propylene glycol. The granule flow was adversely affected when high levels of liquid adjuvants were used in formulations. Wettability study was conducted to measure wetting time for pure drug and the optimized batch. Improved drug dissolution was attributed to improved wetting and the solubilizing effect of adjuvants from the pseudosolid dispersions of nimesulide. Significant improvement in drug dissolution was observed (Q120 = 70%), compared with pure drug powder (Q120 = 15%). In conclusion, dissolution of nimesulide can be modulated using an appropriate blend of pharmaceutical adjuvants.

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation

Abstract This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

Exploration of Melt Granulation Technique for the Development of Coprocessed Directly Compressible Adjuvant Containing Lactose and Microcrystalline Cellulose

The objective of the present investigation was to prepare and evaluate lactose and microcrystalline cellulose based, directly compressible adjuvant using melt granulation technique. The percentage of polymer blend (PVP K 30 and PEG 4000; 5, 10, or 15%) and the polymer blend ratio (9:1, 1:1, or 1:9) were selected as independent variables in a 32 full factorial design. The lactose and microcrystalline cellulose blend (3:1) was mixed with the meltable binder on a water bath at 90°C. The agglomerates were cooled to 35°C and subsequently passed through 30 mesh. A batch containing 12.5% of the polymer blend containing 1:9 ratio of PVP:PEG was used for further studies. In an another 32 full factorial design, disintegrant (crospovidone, croscarmellose sodium, or sodium starch glycolate) and mode of addition of disintegrant (intragranular, extragranular, or combination of intragranular and extragranular) were used as independent variables. The agglomerates were evaluated for percentage fines and Carrs index. Tablets were prepared on a single-punch tablet machine, and they were evaluated for tensile strength, friability, and disintegration time. Regression analysis was carried out to evolve full and refined models. Contour plots are presented for graphical expression of the results. The use of composite index is demonstrated for the selection of an appropriate batch. The disintegration time of tablets reduced from 18 min to 6 min when 6% crospovidone was included in the product. The optimized adjuvant was characterized for particle size distribution, granular friability, Kawakitas and Kunos equation, and dilution potential study. Turmeric, glycyrrhiza, acetaminophen, and metformin HCl were used as model drugs for the preparation of tablets. The present study underlines the fact that melt granulation technique may be adopted for the development of multifunctional directly compressible adjuvant for use in pharmaceuticals. The advantages of melt granulation technique over the classical wet granulation and spray-drying are presented.

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.