Administration of drugs through skin has received great attention through the last decade. Hence this study aims to formulate an anti-histaminic drug-Chlorpheniramine maleate (CPM) as transdermal patch using different bioadhesive polymers such as ethyl cellulose, cellulose acetate, and polyvinyl pyrrolidon with different plasticizers such as propylene glycol (PG) and polyethylene glycol 400 (PEG400). Patches were prepared though solvent evaporation method, evaluated for their physical and mechanical properties and then subjected to stability study to select the best formulae to be evaluated in vitro and in vivo. The selected formulae were examined for CPM release in phosphate buffer saline pH 5.5 and also tested for CPM permeation through ear rabbit skin. Finally, one formula was evaluated in vivo in comparison with multiple oral doses of commercial CPM oral tablets and results showed that CPM transdermal patch has higher bioavailability than an oral tablet of the same dose, with lower plasma fluctuation and less administration frequency.

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Crystallo-co-agglomeration (CCA) is a novel particle engineering/design technique developed by Kadam et al, to overcome the limitations of spherical crystallization (SC). Basically, it's single step process used for size enlargement of single, two or more, small dose or large dose drugs, in combination with or without diluent. The process of CCA involves simultaneous crystallization and agglomeration of drug/s with/without excipients/s from good solvent and/or bridging liquid by addition of a non-solvent. Till date CCA has been applied for spherical agglomeration of talc, bromhexine hydrochloride-talc, ibuprofen-talc, ibuprofen-paracetamol, and naproxen-starch. The spherical agglomerates obtained by CCA can be used as intact beads (encapsulated spansules) or directly compressible tablet intermediates having satisfactory micromeritic (flowability), mechanical (friability, crushing), compressional (compressibility, compactibility), and drug release properties. Modified drug release from agglomerates and compacts thereof can be achieved using suitable polymer composition in the process design. Thus, it can be concluded that, CCA is a simple and cost effective process, which can be tailor-made for particle design of all majority of drugs and combinations thereof.

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The rationale of this investigation was to develop fast dissolving tablets of naproxen sodium using camphor as a subliming agent. Orodispersible tablets of naproxen sodium were prepared by the wet granulation technique using camphor as a subliming agent and sodium starch glycolate together with crosscarmellose sodium as superdisintegrants. Camphor was sublimed from the granules by exposing the granules to vacuum. The porous granules were then compressed into tablets. Alternatively, tablets were first prepared and later exposed to vacuum. The formulations were evaluated for weight variation, hardness, friability, drug content, wetting time, and in vitro dissolution. All the formulations showed low weight variation with dispersion time less than 55 s and rapid in vitro dissolution. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The results revealed that the tablets containing the subliming agent had a good dissolution profile. The drug content of all the formulations was within the acceptable limits of the United States Pharmacopoeia XXVII. The optimized formulation showed good release profile with maximum drug being released at all time intervals. It was concluded that fast dissolving tablets with improved naproxen sodium dissolution could be prepared by sublimation of tablets containing a suitable subliming agent. This work helped in understanding the effect of formulation processing variables especially the subliming agent on the drug release profile.

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The objective of this research was to prepare, characterize, and to study dissolution properties of inclusion complexes of telmisartan (TLM), with β-cyclodextrin and hydroxypropyl-β-cyclodextrin and to study effect of complexation on aqueous solubility and rate of dissolution in dissolution media. The phase solubility curve was classified as an A _P type for both the CDs, which indicated formation of the inclusion complex of TLM in 1:2 stoichiometries with β-CD and HP-β-CD. The inclusion complexes in molar ratio of 1:2 were prepared by various methods. The molecular behavior of TLM in all samples were characterized by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction studies. The result of studies showed inclusion of TLM molecule into cyclodextrin cavities. The highest improvement in in-vitro dissolution of TLM was observed in a complex prepared with HPβ-CD using the kneading method. Mean dissolution time (MDT) and similarity factor (f2) indicated a significant difference between the release profile of TLM from complexes, physical mixture, and pure TLM. The highest improvement in solubility and in-vitro drug release were observed in inclusion complex prepared with HP-β-CD by kneading method. Improvement in solubility and in-vitro drug release of telmisartan was more with HP-β-CD as compared to β-CD

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The release of drug substance from controlled-release dosage forms is often pH-dependent since most drugs are either weak acids or weak bases. A system that permits the drug release to be changed freely while maintaining pH-independent drug release (model drug was Domperidone) was developed. Powder mixture of drug and HPMC K4M, eudragit L100, sodium bicarbonate (as gas-generating agent) and other excipients were mixed and directly compressed using single-punch tablet compression machine. It was found that sodium bicarbonate reacts with HCl and produce carbon dioxide which creates pores in tablet and elevates swelling by wetting the polymer. So it helps in maintaining the buoyancy. The release rate could be modified by varying the polymer ratio. The prepared tablets were evaluated for general appearance, content uniformity, hardness, friability, buoyancy, in vitro drug release and in vivo studies. The best formulation (D ₁ ) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO ₄ . These studies revealed that the tablets remained in the stomach for 250±30 min in fasted rabbits and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs. The linear regression analysis and model fitting showed that all these formulations followed Higuchi model, which had a higher value of correlation coefficient (r). The scanning electron microscopy images of the tablet (D ₁ formulation) were taken before and after dissolution and images showed that the drug was released from matrix by diffusion mechanism. Stability studies of all formulations were carried out at elevated temperature and humidity conditions of 40±2 ^o C/75±5% RH and a control sample was placed at an ambient condition for 12 months. It was found that there was no significant change in buoyancy property as well as in drug content from initial drug content of all the formulations at the end of 12 months, indicating that the formulations are stable.

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The present study was undertaken to prepare direct compressible tablets of nimesulide by altering its physical properties with the help of the method crystallo-co-agglomeration technology. Nimesulide is a widely used nonsteroidal anti-inflammatory drugs type of drug and is very useful in the treatment of arthritis. Because of its poor flowability character, tablets of nimesulide cannot be prepared by direct compression. An attempt has been taken to improve the tableting property by altering the micromeretic properties, like flow rate, Carr index, Hausner ratio and angle of repose. Conformation of improvement of compressibility and other processing problems was studied by Heckel analysis and Kawakita constant using a hydraulic press under a pressure of 0.5, 1, 2 and 4 tonnes for 10 s. The tablets were prepared by direct compression of nimesulide agglomerates using two different types of polymers, polyethelene glycol (PEG6000) and ethyl cellulose (EC) in different ratios (50, 100 and 200 mg). The drug release shows different patterns for the various percentages of PEG and EC.

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The aim of this study was to prepare and characterize nanosuspensions of a poorly soluble drug (Atorvastatin calcium) in order to enhance its solubility and dissolution characteristics. Nanosuspensions were prepared by high pressure homogenization technique. They were characterized by thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), solubility, and in vitro drug release studies. The absence of atorvastatin peaks in PXRD profiles of nanosuspensions suggests the transformation of crystalline drug into an amorphous form. TGA examination suggested that the drug was converted into anhydrous form from the original trihydrate form. DSC curves also compliment the result obtained by TGA and PXRD. The effect of particle size was found to be significant on the saturation solubility of the drug. The in vitro drug release studies showed a significant increase in the dissolution rate of nanosuspensions as compared with pure drug. This study has shown that initial crystalline state is reduced following particle size reduction and that the dissolution characteristics of atorvastatin nanosuspensions were significantly increased in regards to the pure drug. The method being simple and easily scaled up, this approach should have a general applicability to many poorly water-soluble drug entities.

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The solid binary systems of aceclofenac (AC) with β-cyclodextrin (βCD) were prepared by co-grinding, kneading, and co-evaporation, and with PEG 6000 were prepared by the melt-solvent method in 1:1 and 1:2 molar and weight ratios, respectively. The phase solubility study with βCD suggested B _S type of curve with a possibility of 1:1 inclusion complex. The solid systems were characterized by in vitro release studies, DSC, and SEM. The results of solid state studies revealed that AC was completely dissolved in the carrier matrix in case of the melt-solvent method, which suggested the possible formation of solid solution with AC to be existed in an amorphous state. All the binary systems exhibited improved dissolution as compared to pure drug. However, the best dissolution enhancement was achieved with the binary system AC: PEG 6000 in 1:2 weight ratio using the melt-solvent method which was subjected to tablet preparation by direct compression. The tablets so compressed complied with in-house and compendial specifications. The in vitro dissolution test was carried out for the formulated tablets and three popular marketed brands of conventional AC tablets. None of the commercial brands showed complete drug release but the formulated tablets exhibited almost complete drug release within 50 min. The dissolution data were further characterized using model-independent parameters DP ₃₀ , DE ₅₀ , t _50% , similarity factor f2 and difference factor f1 . The tablets formulated incorporating the AC: PEG 6000 (1:2) binary system displayed significantly improved dissolution profile as compared to existing immediate release commercial tablets.

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The goal of the present study is to evaluate the influence of the formulation and operating conditions on pellet preparation by the pan technique. The effect of initial core weight on the physical parameters of pellets as well as to conduct stability study was also the goal of this study. For this domperidone maleate was selected as the model drug. Pellets were prepared by layering of powdered drug on sugar-based cores. Inert cores were intermittently treated with micronized drug powder and binding solution. This treatment led to the formation of multiple layers of drug particles around an inert core resulting in the production of pellets that can further be coated by different polymers to obtain modified release formulations. Scanning electron microscopy was employed to image the surface morphology of the prepared pellets. Drug loading efficiency, % yield, size, and shape uniformity of pellets were increased along with increasing the initial core weight. Drug content and dissolution study were performed by following HPLC and UV-Visible method. About 50% and 80% drug was released within 7.72 m and 13.66 m respectively in 0.1N HCl media (pH 1.2). Physical appearance of the prepared pellets, potency, moisture content, pellets size and shape, dissolution data, release rate constant, diffusion exponent (P<.05) over the stability period showed that the system is efficient for the production of highly stable formulations. This study also showed the good performance of the conventional coating pan system in obtaining instant release domperidone pellets prepared by the powder layering technique.

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Based on a large number of experiments on solubilization of poorly water-soluble drugs, the author is of the opinion that hydrotropy is another type of cosolvency and all water-soluble substances whether liquids, solids, or gases may act as solubilizers for poorly water-soluble drugs. In the present investigation, a mixed-solvency approach has been utilized for solubility enhancement of poorly water-soluble drug, salicylic acid (as a model drug). Sixteen blends (having total 40% w/v strength of solubilizers) containing various solubilizers among the commonly used hydrotropes (urea and sodium citrate), cosolvents (glycerin, propylene glycol, PEG 300 and PEG 400), and water-soluble solids (PEG 4000 and PEG 6000) were made to study the influence on solubility of salicylic acid. Twelve blends were found to increase the solubility of salicylic acid, synergistically. This approach shall prove a boon in pharmaceutical field to develop various formulations of poorly water-soluble drugs by combining various water-soluble excipients in safe concentrations to give a strong solution (say 25% w/v or so) to produce a desirable aqueous solubility of poorly water-soluble drugs. In the present investigation, the mixed-solvency approach has been employed to analyze salicylic acid in the bulk drug sample (using six blends) precluding the use of organic solvents (a way to green chemistry).

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Mucoadhesive tablets were prepared to evaluate the adhesive property of the gum obtained from seeds of Ceaselpinia pulcherrima (CP) by comparing it with carbopol, hydroxy propyl methylcellulose (HPMC), and Chitosan. Physical parameters such as bulk density, tapped density, compressibility index, and Hausner's ratio values indicate good flow, the percentage of drug content was in the range of 96.4± 0.97%, and various adhesive evaluation results reveal a good mucoadhesive property. The barium sulphate loaded tablet possesses strong mucoadhesive property, which was evident from prolonged adhesion in the same location of the stomach up to a period of 10 h, whereas the duration of adhesion found to be comparatively less with other polymers. From the results of in vitro and in vivo adhesive tests and in vitro release study the test agent (Gum) appears to exhibit considerable mucoadhesive property and mean residence time values when compared with tablets of carbopol, HPMC, and Chitosan.

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The electrostatic interaction between oppositely charged polyelectrolytes leads to formation of insoluble polyelectrolyte complexes in aqueous medium. The polyelectrolyte complexes formed between a polyacid and a polybase are little affected by the pH variation of the dissolution medium. In the present study attempts were made to prepare polyelectrolyte complexes of polyvinyl pyrrolidone (polybase) and carbopol (polyacid) into which diclofenac sodium is incorporated and studied for its controlled release. The polyelectrolyte complexation was evaluated by pH, conductivity, Fourier transformed infrared spectroscopy, and X-ray difractometry. The dried polyelectrolyte complexes were also evaluated for micromeritic properties and drug release kinetics. Selected PECs were compressed into tablets and compared with commercial SR product for drug release. The tablets showed comparable results with commercial SR product following zero-order release, and drug release is by erosion as well as the diffusion mechanism. Promising results were obtained suggesting the application of these polyelectrolyte complexes in the design of controlled release systems.

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Transdermal patches of papaverine hydrochloride were prepared by the solvent casting method using ethyl cellulose: PVP, PVA: PVP and Eudragit RL-100: Eudragit RS-100 using different ratios. The physicochemical parameters such as flexibility, thickness, smoothness, weight variation, moisture content, hardness and tensile strength were evaluated for the prepared patches. The formulation exhibited flexibility, uniform thickness and weight, smoothness, good drug content (92 to 96%), and little moisture content. The in vitro diffusion studies were carried out using modified Keshery-Chein cell using cellophane as the diffusion membrane and the formulation followed the Higuchi diffusion mechanism. The formulation containing PVA: PVP as polymers showed faster release rate (hydrophilic polymers) compared to Eudragit RL-100: Eudragit RS-100 (hydrophobic polymers) or combination of hydrophilic and hydrophobic polymers (ethyl cellulose and PVP). The stability studies indicated that all the patches maintained good physicochemical properties and drug content after storing the patches in different storage conditions. Compatibility studies indicated that there was no interaction between the drug and polymers. In vivo studies showed that papaverine hydrochloride helps in decreasing the effect of isoproterenol-induced myocardial necrosis. Hence, the aim of the present study was to prepare the sustained release formulation (Transdermal patches) of the drug using different blend of polymers. The formulated patches containing the hydroplilic polymers showed best release rate of drug.

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