Atazanavir-Concentrate Loaded Soft Gelatin Capsule for Enhanced Concentration in Plasma, Brain, Spleen, and Lymphatics.

This study investigates the development of atazanavir-concentrate loaded soft gelatin capsule for achieving enhanced atazanavir (ATV) concentration in plasma, brain, spleen, and lymphatics beneficial in the significant reduction of viral load in HIV infection. For this purpose, ATV-concentrate in the presence and absence of Soluplus with corn oil, oleic acid, tween 80, and propylene glycol was developed. The developed ATV-concentrate was found to have enhanced dispersibility with no signs of precipitation after dilution with simulated G.I fluid as evident from particle size (16.49±0.32 nm) and PDI (0.217±0.02) analysis. The rheological and molecular docking studies explainedthe reduction of viscosity of SuATV-C due to the intermolecular H-bond between ATV and Soluplus that helps to retard crystallization. The shell of the soft gelatin capsule retains its integrity when subjected to a folding endurance test on a texture analyzer depicting that the concentrate did not affect the integrity of the soft gelatin capsule shell. An ex vivo and in vivo pharmacokinetic study in rats revealed that the SuATV-C soft gelatin capsule (SuATV-C SGC) indicated 2.9 fold improvement in rate and extent of permeation and absorption than that of ATV-suspension. The tissue distribution study also exhibited higher drug concentration in the brain (2.5 fold), lymph nodes (2.7 fold), and spleen (1.2 fold) administered with SuATV-C SGC, revealing the overwhelming influence of Soluplus and corn oil. In a nutshell, these studies demonstrated that SuATV-C SGC seems to have the potential to deliver an anti-retroviral drug to the viral sanctuaries for the better management of HIV.

Assessing the viability of carbamoylethyl pullulan-g-stearic acid based smart polymeric micelles for tumor targeting of raloxifene.

The present investigation entails the synthesis of smart pullulan polymeric micelles for evaluating its tumor targeting potential. For this purpose, two step polymerization synthesis reactions were conducted. In the first step, carbamoylethylation occurs by reaction of the free alcoholic moieties at 6th position of glucopyranose unit of pullulan with acrylamide in presence of alkali to obtain carbamoylethyl pullulan (CmP). In the second step, CmP undergoes graft polymerization with stearic acid (SA) to obtain CmP-g-stearic acid diblock co-polymer (CmP-g-SA) as evident from FTIR and NMR analysis. The XpRD spectra showed crystalline nature that was further confirmed by SEM indicating rough and poly-porous morphology. The QbD based optimized formulations of raloxifene HCl (RLX) loaded polymeric micelles (RLX PMs) exhibited pH-dependent release profile with added advantage of 1.2 times reduction in percentage hemolysis giving substantial compatibility with erythrocytes. In vivo pharmacokinetic performance of RLX PMs suggested enhanced mean residence time and volume of distribution. Besides, the biodistribution study of RLX PMs manifested enhanced entry of RLX in mammary carcinoma tissues as compared to normal tissues suggested that CmP-g-SA based micelles enhanced the anti-tumor activity of RLX. Overall, the findings pointed toward the biocompatibility of CmP-g-SA as a potential carrier system for the delivery of RLX.

Containment of varicella outbreak in intensive care unit of a tertiary level hospital.

BACKGROUND: Varicella-Zoster virus (VZV) infection in healthcare organizations, especially in intensive care units (ICU), having admitted immunocompromised patients, is of serious concern as well as poses threat to healthcare workers working in such critical areas. The present report defines the transmission and infection control measures initiated to curtail VZV infection spread in the trauma ICU of a tertiary care hospital of North India. OUTBREAK REPORT: At the infection outset, there were 12 patients admitted in ICU and 54 healthcare workers were posted to manage these critical patients. After confirmation of VZV infection, all susceptible patients as well as healthcare workers were quarantined and fresh intake of patients was restricted. Out of the total healthcare workers, 14 (25.92%) were found susceptible (as per protective VZV IgG titers) and were vaccinated. Of the 12 patients admitted in the ICU, six patients were discharged and sent home directly, four patients expired due to their critical disease state, one patient left against medical advice, and one patient remained admitted in ICU till the incubation period was over. Epidemiologically, line listing for index case reporting was done. The efficacy of control measures was re-evaluated to strengthen existing infection control practices and general measures viz. strict hand washing, adherence to aseptic protocols and intensification of environmental cleaning. CONCLUSIONS: Established varicella surveillance measures ensure VZV outbreaks are identified in a timely manner and control measures implemented to prevent further transmission. Also, vaccination policy among HCWs is the utmost requirement despite having huge financial implications.

Investigating the potential of carboxymethyl pullulan for protecting the rabbit eye from systematically induced precorneal tear film damage.

The present investigation was aimed to develop a rabbit model for protecting the rabbit eye from systematically induced precorneal tear film (PTF) damage, evaluation of carboxymethyl pullulan for its protective action against PTF damage and its curative potential. For the same, pullulan was modified by carboxymethylation and structural modification was confirmed by spectral attributes. Further, the carboxymethyl pullulan (CMP) solutions (0.1-2.0%, w/v) were evaluated for their physical properties and its concentration 1.5% (w/v) was found to fit the criterion to prepare an eye solution. The safety and non-toxicity of CMP (1.5%, w/v) eye solution was confirmed by HET-CAM method and rabbit eye irritation test. Further, a systematic rabbit eye model was developed that mimic PTF damage in day to day life. Therefore, three levels of PTF damage were developed equating symptoms of damage due to high temperature (level I) or long term mobile use (level II) or heavy air pollution (level III). Thus, a representative model with benzalkonium chloride (BAC, 0.1% v/v, 0.2% v/v and 0.3% v/v), administered two drops twice a day for two days to develop level I, level II and level III eye damage. The CMP (1.5%, w/v) eye solution possessed a protective potential against level I and II PTF damage. The rabbit eyes remained unharmed and comparable with the normal control during the complete experimental period. Additionally, CMP (1.5%, w/v) eye solution has shown early fast recovery (8 days) from PTF damage induced by instillation of PTF damage agent (BAC). Carboxymethyl pullulan eye protective solution has normalized the tear film stability in rabbit eye model. It is established from the present work that, carboxymethyl pullulan has protective action against precorneal tear film damage and it potentiates the early recovery too.

QbD-Based Development of Cationic Self-nanoemulsifying Drug Delivery Systems of Paclitaxel with Improved Biopharmaceutical Attributes.

The present studies describe quality-by-design-based design and characterization of cationic self-nanoemulsifying formulations of paclitaxel for improving its biopharmaceutical attributes. Solubility and phase titration experiments were designed to select the lipidic and emulsifying excipients. Two different types of lipidic nanoformulations were developed using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). The nanoformulations were optimized by mixture designs and subjected to evaluation for globule size, zeta potential, drug release, and intestinal permeability. Following apt mathematical modeling, the optimum nanoformulation was earmarked using numerical optimization. Further, cationic formulations were developed for both LCT- and MCT-containing formulations and subjected to performance evaluation. The optimized formulations were extensively evaluated, where an in vitro drug release study indicated 2.7-fold improvement in dissolution rate from optimized cationic nanoformulations over powder pure drug. Ex vivo and in situ evaluation performed on Wistar rats exhibited nearly six- to eightfold enhancement in permeation and absorption parameters of the drug for the optimized cationic nanoformulation as compared to the pure paclitaxel. Pharmacokinetic studies indicated nearly 13.4-fold improvement in AUC and Cmax, along with 1.8-fold reduction in Tmax of the drug from cationic nanoformulations as compared to the pure drug suspension. Moreover, nanoformulation containing long-chain lipids exhibited superior performance (1.18-fold improvement in drug absorption) over medium-chain lipids. Cytotoxicity evaluation of cationic nanoformulations on MCF-7 cells revealed significant reduction in growth vis-à-vis the pure drug. Overall, the current paper reports successful systematic development of paclitaxel-loaded cationic self-nanoemulsifying systems with distinctly improved biopharmaceutical performance.

Formulation optimization of aprepitant microemulsion-loaded silicated corn fiber gum particles for enhanced bioavailability.

The present investigation was aimed at development of silicate corn fiber gum (SCFG) particles as superior solid carrier for the preparation of Aprepitant (APT)-loaded self-emulsifying powder (SEP) system. 2(4) D-optimal mixture design with three level process variables was employed to develop SCFG particles, utilizing flow descriptors and hydrophobicity descriptors as response variables. The results indicated that blending of CFG (51.4% w/w) and magnesium silicate (MS) (48.6% w/w) using freeze-drying technique was found to have highest desirability (0.904). The developed SEP showed highest oil desorbing capacity, low self-emulsification time and highest drug content. It was observed that SCFG-SEP (F2 formulation) showed lowest PDI (0.2445 ± 0.03) as well as smallest particle size (127 ± 5.8 nm). The droplets were uniform and maintain their integrity after reconstitution (TEM analysis). Furthermore, APT-loaded SEP showed enhanced in vitro dissolution (4 folds) and ex vivo performance (7-fold enhanced Papp) as compared to pure APT. Furthermore, in vivo pharmacokinetic study showed that significant enhancement (p > 0.05) in Cmax was evident with APT-loaded F2 (SCFG-SEP) (1.93-fold) and F4 (Aerosil 200-SEP) (1.58-fold). The data also suggested increase in absorption rate when APT incorporated into SCFG-SEP. Thus, findings pointed toward enhanced bioavailability of APT when loaded into SCFG particles. Overall, the developed SCFG particles could be considered as a better alternative to already available solid carrier(s).

Low-current operations in 4F(2)-compatible Ta2O5-based complementary resistive switches.

Complementary resistive switches (CRS), which consist of two anti-serially connected bipolar switching ReRAM cells, can reduce sneak path currents in passive crossbar arrays. However, the high operation current restrains the implementation of the CRS device. In this article, we present low current operation (<300 µA) of vertically stacked, 4F(2)-compatible Ta2O5-based CRS devices exhibiting two terminals. Two types of devices, either offering a nano- or a micrometer scale bottom cell (BC), are considered. The top cell (TC) in both configurations is designed of micrometer size. A novel three-step electroforming procedure for the vertical CRS device having no access to the middle electrode is exemplified and compared to the conventional forming procedure using three-terminal CRS devices. This three-step electroforming procedure provides adjustment of the maximum switching current in the nano-BC CRS: a low-level current compliance during forming enables low current CRS operation in subsequent switching cycles. Further, the nano-BC CRS shows the stable switching up to 10(4) cycles whereas the micro-BC CRS endures up to 10(6) cycles.

Exploiting the interaction of polymethacrylates with iron oxide for the enhancement of mucoadhesive strength.

The present investigation was aimed at preparation of polymethacrylate(s)- iron oxide conjugates and to evaluate mucoadhesive performance using texture analyzer. Eudragit RL-iron oxide or Eudragit RS-iron oxide conjugate granules were prepared by solvent evaporation technique. The mucoadhesive strength of pure Eudragit RL and RS was found to be 11.25±2.02 and 7.78±0.92 g respectively, whereas the same was found to be 36.42±4.01 and 24.32±4.44 for the iron oxide conjugates of Eudragit RL and RS respectively. Hence, mucoadhesive strength of polymethacrylates was found to be enhanced by this technique while, retaining their pH resistant property. A correlation (p>0.05) of 0.97 between mucoadhesive strength and zeta potential indicated conjugation of iron oxide contributed positive surface charge that causes enhancement of mucoadhesion. Further, the ATR-FTIR spectral analysis as well as DSC analysis supported existence of ionic interactions between conjugates (Eudragit RS or RL with iron oxide) and the tissue surface. Hence, the findings point out toward the expected potential use and application of Eudragit RL-iron oxide conjugate in mucoadhesive drug delivery systems, gastro retentive drug delivery systems, etc.

N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and Their Pharmacological Implication: A Medicinal Chemistry-Oriented Perspective Outline.

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc.). Additionally, reported NMDA antagonists from different sources, such as synthetic, semisynthetic, and natural resources, are explained by their mechanism of action and pharmacological role. The comprehensive report also addresses the chemical spacing of NMDA inhibitors and in-vivo and in-vitro models to test NMDA antagonists. Since the Blood-Brain Barrier (BBB) is the primary membrane that prevents the penetration of a wide variety of drug molecules, we also elaborate on the medicinal chemistry approach to improve the effectiveness of their antagonists.

Molecular weight determination and correlation analysis of Dalbergia sissoo polysaccharide with constituent oligosaccharides.

INTRODUCTION: Mucilaginous polysaccharide extracted from Dalbergia sissoo Roxb. leaves has a number of medicinal applications. Molecular weight studies and correlation analysis of the structure of polysaccharide with oligosaccharides can be helpful for further utilisation, modification and structure-activity relationship for biological applications. OBJECTIVE: To determine molecular weight of medicinally important polysaccharide. To establish an unequivocal correlation of the polysaccharide monosugars with constituting oligosaccharides and glucuronic acid content based on gas-liquid chromatography (GLC) with the spectrophotometric method. METHODOLOGY: Complete and partial hydrolytic studies of pure polysaccharide yielded constituting monosugars and oligosaccharides. The ratio of sugars in polysaccharide and oligosaccharides was studied by preparation of alditol acetates and analysed using GLC. The uronic acid content was studied by GLC analysis and spectrophotometry. Molecular weight of the polysaccharide was determined using the viscometric method. RESULTS: Dalbergia sissoo leaves yielded 14.0% pure polysaccharide, containing 15.7% of glucuronic acid. Complete hydrolysis and GLC analysis of alditol acetate derivatives of reduced and unreduced monosugars indicated the presence of L-rhamnose, D-glucuronic acid, D-galactose and D-glucose in 1.00:1.00:2.00:2.33 molar ratios. Partial hydrolysis followed by monosugar analysis of oligosaccharides established the monosugar ratio in complete agreement with polysaccharide, thereby corroborating the sugar ratio. Similar uronic acid content was obtained by GLC and spectrophotometry. The polysaccharide had an average molecular weight of 1.5 × 105 Da. CONCLUSION: The study has established an obvious correlation of the structure of polysaccharide with oligosaccharides, leading to unambiguous identification of monosaccharides, which normally is not studied conclusively while reporting the polysaccharide structure. The molecular weight of the polysaccharide was determined.

In silico-assisted development of supersaturable preconcentrated isotropic mixture of atazanavir for augmenting biopharmaceutical performance in the presence of H2-receptor antagonist.

The therapeutic potential of atazanavir (BCS Class II drug), a highly selective inhibitor of human immunodeficiency virus (HIV-1), has been largely limited due to its low intrinsic solubility at elevated pH resulting in low oral bioavailability. Thus, the current work describes the systematic development, optimization, and evaluation of hydroxypropyl methylcellulose acetate succinate (HPMC-AS)-based supersaturable preconcentrate isotropic mixture (SP-IM) containing long-chain triglyceride to improve intestinal lymphatic transport and augment oral bioavailability of atazanavir (ATZ). A D-optimal mixture design was employed for optimization of plain IM containing corn oil, oleic acid, Tween 80, and propylene glycol, evaluating various critical quality attributes (CQAs) like particle size, polydispersity index, self-emulsification time, % transmittance, and drug content. In silico analysis and in vitro supersaturation test facilitated the selection of HPMC-AS as a best suited polymeric precipitation inhibitor (PPI) for formulating ATZ loaded SP-IM (ATZ-SP-IM). In vitro dissolution data indicated that ATZ-SP-IM exhibits superior performance in 0.025 N HCl and pH 6.8 over pure drug. Ex vivo permeation and in vivo pharmacokinetic study of ATZ-SP-IM corroborated enhanced permeation (2.03 fold) and improved drug absorption via lymphatic transport in Wistar rats. Further, the pharmacokinetic performance of ATZ-SP-IM was not affected in presence of H2 receptor antagonist. Therefore, the results showed that ATZ-SP-IM can significantly improve the biopharmaceutical attributes of ATZ so as to lay a foundation of further research on the new dosage form of ATZ.

Preparation and Characterization of Clopidogrel Bisulfate-hydroxypropyl-ß-Cyclodextrin Mixed Inclusion Complex for Improved Intestinal Solubility and Anti-Thrombotic Efficacy.

The study aimed to increase the intestinal solubility and absorption of orally bioavailable clopidogrel-bisulfate (CPB) by complexing with hydroxypropyl-ß-cyclodextrin (HCD) to form a binary inclusion complex that was stabilized by Tween 80 (T80) resulting into mixed inclusion complex. The results of phase solubility studies and molecular docking of CPB with ß-cyclodextrin (ß-CD) and HCD suggested higher solubility and binding energy of the stable CPB: HCD complex in the presence of T80 as compared to the CPB: ß-CD complex. The D-Optimal mixture design was used to optimize the formulation containing the CPB: HCD: T80 mixed inclusion complex. The results suggest the enhanced stability of the CPB: HCD inclusion complex in the presence of T80. The spectral attributes confirmed the inclusion complexation and pointed out the central position of CPB in a hydrophilic cavity of HCD. Further, the prepared soft gelatin capsule successfully confirmed the importance of obliterating the intestinal precipitation associated problem of CPB through an in-vitro release study. The anticoagulant activity in rabbits confirmed that soft gelatin capsules showed 1.2 folds and 1.3 folds increase in clotting time, 1.2 fold and 1.5 folds increase in bleeding time when compared to marketed formulation and pure drug, respectively. Conclusively, soft gelatin capsules exhibit the potential to enhance the oral bioavailability of CPB, leading to reduction of the dose and dose-related side effects.

Navigating the landscape of psoriasis therapy: novel targeted pathways and emerging trends.

INTRODUCTION: Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics. AREA COVERED: This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms. EXPERT OPINION: A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.

Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing.

Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-ß, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.

Effect of substrates on structural and optical properties of tin oxide (SnO2) nanostructures.

We report on controlling the morphology of tin oxide (SnO2) nanostructures and the study of the effect of surface morphology on structural and optical properties of SnO2 nanostuctures. In present work, Tin oxide (SnO2) nanostructures such as nanowires and nanorods have been grown by thermal evaporation of SnO2 powder. To demonstrate the effect of different substrates on the morphology of grown SnO2 nanostructures, the thermal evaporation of SnO2 powder was carried out on Si and gold catalyzed Si (Au/Si) substrates. The scanning-electron-microscopic analysis shows the growth of SnO2 nanowires on Au/Si substrate and growth of SnO2 nanorods on Si substrate. The scanning-and transmission-electron-microscopic analysis shows that the diameter of SnO2 nanowires and nanorods are about 70 nm and 95 nm respectively and their length is about 80 microm and 30 microm respectively. The vapor-liquid-solid (VLS) growth of SnO2 nanowires and vapor-solid (VS) growth of SnO2 nanorods is also confirmed with the help of TEM and EDX spectra. The synthesized SnO2 nanowires show tetragonal rutile structure of SnO2, whereas SnO2 nanorods show tetragonal rutile as well as cassiterite structure of SnO2. UV-Vis absorption spectra showed the optical band gaps of 4.1 eV and 3.8 eV for the SnO2 nanowires and the nanorods, respectively. The SnO2 nanowires and nanorods show photoluminescence with broad emission peaks centred at around 600 nm and 580 nm respectively. Raman spectra of SnO2 nanowires shows three Raman shifts (478, 632, 773 cm(-1)) corresponding to Eg, A1g and B2g vibration modes, whereas in Raman spectra of SnO2 nanorods, A1g peak is dramatically reduced and the B2g mode is totally quenched.

Chitosan films: crosslinking with EDTA modifies physicochemical and mechanical properties.

The present study was aimed to develop chitosan-EDTA films and evaluate their physico-chemical and mechanical properties. The physical properties suggested lowest swelling, volume and volume index of films prepared by employing equal weight of chitosan (CH) and EDTA (1.5% w/v). The CH:EDTA film (1:l, on weight basis) showed minimum contact angle, work of adhesion and high negative spreading coefficient indicating lipophilic behavior of film. Further, the FTIR and DSC analysis suggested maximum crosslinking density in film prepared with equal proportion of CH and EDTA. The mechanical properties explored using texture analyzer revealed increasing the proportions of EDTA rendered the films more flexible and decreased their hardness. Furthermore, in vitro permeation of 5-FU and mesalamine with different solubilities showed minimum permeation across CH­EDTA (1:1) film, indicating high crosslinking density that decreased void space inside the film. Hence, the CH­EDTA conjugate could be considered to be possess great potential for various pharmaceutical applications such as film based delivery systems, controlled and sustained delivery systems etc.

Optimization of an aqueous tablet-coating process containing carboxymethylated Cassia fistula gum.

The present investigation was aimed at developing and optimizing a simple aqueous tablet-coating formulation and its process. 5-Fluorouracil (5-FU) was used to ascertain the relative lipophilic/hydrophilic behavior of the coating system. Optimization was performed by evaluating the adhesive force strength and cohesive force strength of the tablet coat using a texture analyzer. The in vitro release of 5-FU was found to decrease with an increase in (tablet surface-coat) adhesive force strength. The (tablet-tablet) cohesive force strength was reduced by the addition of magnesium silicate to the coating solution. The addition of magnesium silicate (0.2% w/v) to the carboxymethyl Cassia fistula gum-chitosan (CCG-CH) coating surface significantly inhibited the release of 5-FU possibly due to an increase in the hydrophobic character of the coated tablet surface. This was possible by coating cohesive force strength reduction coating compositions (CCG-CH (70:30) and 0.3% magnesium silicate). Further, the FTIR-ATR and DSC analyses suggested the pivotal role of magnesium silicate in modifying the release of 5-FU from CCG-CH-coated tablets due to hydrogen bonding of its Si-O-Si or Mg-O groups with -OH moieties of CCG-CH.

Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

Fabrication and optimization of fast disintegrating tablets employing interpolymeric chitosan-alginate complex and chitin as novel superdisintegrants.

The objective of the present work was to optimize the formulation of fast disintegrating tablets (FDTs) of ondansetron HCl containing novel superdisintegrants, possessing sufficient mechanical strength and disintegration time comparable to those containing crospovidone or croscarmellose sodium. The FDTs were formulated using a novel superdisintegrant (chitosan-alginate (1:1) interpolymer complex and chitin) to achieve a sweet tasting disintegrating system. The results revealed that chitin (5-20%) increased the porosity and decreased the DT of tablets. At higher concentrations chitin maintained tablet porosity even at 5.5 kg crushing strength. Ondansetron HCl was found to antagonize the wicking action of glycine. Further, evaluation of the mechanism of disintegration revealed that glycine transported the aqueous medium to different parts of the tablets while the chitosan-alginate complex swelled up due to transfer of moisture from glycine. This phenomenon resulted in breakage of the tablet within seconds. For preparing optimized FDTs, the reduced model equations generated from Box-Behnken design (BBD) were solved after substituting the known disintegration time of FDTs containing superdisintegrants in the reduced model equations. The results suggested that excipient system under investigation not only improved the disintegration time but also made it possible to prepare FDTs with higher crushing strength as compared to tablets containing known superdisintegrants.