Nomogram for computing the value of similarity factor.

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

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. KEY FINDINGS: Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. SUMMARY: Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.

Advanced formulation design of venlafaxine hydrochloride coated and triple-layer tablets containing hypromellose.

The purpose of this research work was to develop venlafaxine hydrochloride-coated and layered matrix tablets using hypromellose adopting wet granulation technique. The granules and the tablets were characterized. The monolithic tablets were coated with different ratios of ethyl cellulose and hypromellose. The in vitro dissolution study was performed in distilled water. In the layered tablets, the middle layer containing drug was covered with barrier layers containing high viscosity grade hypromellose. Simplex lattice design was used for formulating the layered tablets. The dissolution study of the optimized batches and a reference product was carried out in 0.1 N HCl, phosphate buffer and hydroalcoholic solution. Burst drug release was exhibited by the uncoated tablets, probably due to high aqueous solubility of venlafaxine HCl. The coated tablets showed sustained drug release without burst effect. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the coated tablets. The layered tablets also exhibited sustained release without burst effect due to effective area reduction. The optimized batches showed identical drug release in 0.1 N HCl, phosphate buffer and 10% v/v aqueous alcohol. Layered tablets may well be adopted by the industry due to the possibility of achieving a high production rate.

Fabrication of triple-layer matrix tablets of venlafaxine hydrochloride using xanthan gum.

The objective of present investigation was to develop venlafaxine hydrochloride-layered tablets for obtaining sustained drug release. The tablets containing venlafaxine hydrochloride 150 mg were prepared by wet granulation technique using xanthan gum in the middle layer and barrier layers. The granules and tablets were characterized. The in vitro drug dissolution study was conducted in distilled water. The tablets containing two lower strengths were also developed using the same percentage composition of the middle layer. Kinetics of drug release was studied. The optimized batches were tested for water uptake study. Radar diagrams are provided to compare the performance of formulated tablets with the reference products, Effexor XR capsules. The granules ready for compression exhibited good flow and compressibility when xanthan gum was used in the intragranular and extragranular fractions. Monolayer tablets failed to give the release pattern similar to that of the reference product. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the formulated tablets. Lactose facilitated drug release from barrier layers. Substantial water uptake and gelling of xanthan gum appears to be responsible for sustained drug release. The present study underlines the importance of formulation factors in achieving same drug release pattern from three strengths of venlafaxine hydrochloride tablets.

Studies in preparation and evaluation of pH-independent sustained-release matrix tablets of verapamil HCl using directly compressible Eudragits.

The objective of the present study was to investigate the impact of formulation factors on the properties of a 12h modified-release formulation of verapamil HCl. A 2(3) full factorial design was employed to investigate the influence of amount of Eudragit RS PO/RL PO (X1, a matrixing agent), HPMC K4M (X2, an auxiliary matrixing agent cum binder) and PEG 4000 (X3, channelling agent cum plasticizer). The tablets were prepared by direct compression and they were evaluated for in vitro dissolution studies in 0.1 N HCl. The time required for 90% of the drug release (t90) and similarity factor (f2) were used as responses for the selection of most appropriate batches. Swelling and fluid penetration studies were carried out in 0.1 N HCl. Time required for 90% of the drug release (t90) was calculated by using an appropriate kinetic model for each batch. An ideal drug release profile (i.e., 25% in the first hour and a constant drug release thereafter) was considered as a reference release profile for calculation of f2. Multiple regression analysis was adopted to evolve refined models for t90. The required release pattern was shown by batches containing a low level of Eudragit RS PO/RL PO (30% w/w), low level of HPMC K4M (10% w/w), and high level of PEG 4000 (15% w/w). Response surface plots are shown for t90. These formulations showed slower drug release in alkaline medium (pH 7.2). Succinic acid and KH2PO4 were incorporated in the matrix in order to obtain pH-independent drug release. Swelling of tablets and fluid penetration in the matrix were found to be influenced by the selected independent variables. This study demonstrates that the desired drug release pattern can be obtained by adopting a systematic formulation approach.

Development of agglomerated directly compressible diluent consisting of brittle and ductile materials.

The objective of this investigation was to develop a novel multifunctional coprocessed adjuvant consisting of three known diluents that show different consolidation mechanisms. The method of wet granulation was adopted for the preparation of coprocessed product. Microcrystalline cellulose (MCC) and colloidal silicon dioxide (X1), lactose monohydrate (X2), and dibasic calcium phosphate dihydrate (X3, DCP) were used as independent variables in a simplex lattice design. Croscarmellose sodium was used at 4% level intragranularly in all the batches. The granules (44/120 #) were characterized for angle of repose, bulk density, tapped density, and Carr's index. The tablets of coprocessed adjuvants were characterized for crushing strength, friability, and disintegration time. Multiple linear regression was adopted for evolving refined mathematical models. A checkpoint batch was prepared and evaluated for particle size distribution, moisture uptake, and dilution potential by using nimesulide as a model drug. Microcrystalline cellulose shows poor flowability due to irregular shape and interlocking. Moreover, it loses a part of its compactibility on wet granulation. To attend these problems, a physical blend of 97% microcrystalline cellulose and 3% colloidal silicon dioxide M5 was prepared and used. The blend of MCC and colloidal silicon dioxide showed better flow than that of the original MCC. Hence, it may be easier to mix with lactose and dibasic calcium phosphate. The loss in compactibility of microcrystalline cellulose on wet granulation was also reduced due to presence of colloidal silicon dioxide. As expected, all the batches exhibited acceptable angle of repose (<35 degrees) and quick disintegration (<1 min). Full and refined models for Carr's index and crushing strength were evaluated. Based on the results of grid analysis, a checkpoint (50% MCC, 40% lactose, and 10% DCP) that satisfies both the conditions of Carr's index and crushing strength was selected. The adjuvants absorb very little moisture in the moisture uptake study. The results of dilution potential study reveal that up to 30% nimesulide, a poorly compressible drug, can be incorporated in the coprocessed product. In vitro drug dissolution from capsules containing pure drug powder and compressed tablets was comparable (f2 = 79). The results reveal that the desired product characters can be obtained by varying the quantity of MCC (a ductile material that undergoes plastic deformation), lactose (brittle material with low-fragmentation propensity), and DCP (brittle material with high-fragmentation propensity).