Co-drug of isoniazid and sulfur containing antioxidant for attenuation of hepatotoxicity and treatment of tuberculosis.

The prolonged use of isoniazid (INH) - a highly effective drug in the treatment of tuberculosis - causes fatal liver injury. In order to overcome this adverse effect, a unique amide codrug was designed by covalently linking INH with sulfur-containing antioxidant- alpha-lipoic acid for possible hepatoprotective and antimycobacterial effect. Co-drug LI was prepared by Schotten Baumann reaction and was characterized by spectroscopic analysis. To check the bioreversibility of LI, in vitro release tests were conducted in buffers of specific pH, stomach, and intestinal homogenates of rat employing HPLC. Male Wistar rats were used for the evaluation of the hepatoprotective activity. Liver function markers, oxidative stress markers, and biochemical parameters were estimated. The antimycobacterial efficacy of LI was examined in terms of its ability to decrease the lung bacillary load in Balb/c mice infected intravenously with Mycobacterium tuberculosis. LI resisted hydrolysis in buffers of pH 1.2 (acidic), pH 7.4 (basic), and stomach homogenate of the rat while displayed significant hydrolysis (88.19%) in intestinal homogenates over a period of 6 h. The effect of LI on liver function, antioxidant and biochemical paradigms was remarkable as it reestablished the enzyme levels and restored hepatic cytoarchitecture representing its abrogating effect. The findings of antimycobacterial activity assessment evidently demonstrated that LI was as potent as INH in lowering the mycobacterial load in mice. The outcome of this exploration confirmed that the described co-drug can offer desirable safety and therapeutic benefit in the management of tuberculosis.

Development of High-Strength Extended-Release Multiparticulate System by Crystallo-co-agglomeration Technique with Integration of Central Composite Design.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively. Ethyl cellulose 10 cps was used to improve the strength of agglomerates and achieve extended release. Design of experiment (rotatable central composite design) was implemented for the elucidation of the effect of type and quantity of polymers on quality attributes of agglomerates. Prepared agglomerates were evaluated for morphological, micromeritic, mechanical, and drug release properties. A satisfactory yield (> 97%, wt/wt), better crushing strength, and low friability of agglomerates indicated good processing and handling characteristics. Compatibility and reduced crystallinity of indapamide in agglomerates were confirmed by spectroscopic and X-ray diffraction studies. Formation of the miniscular dosage form and hydrophobicity of talc were the key factors observed in controlling and extending the drug release (up to 6 h) from agglomerates. Hence, the developed crystallo-co-agglomeration technique could be successfully used for the preparation of directly compressible high-strength extended-release spherical agglomerates of indapamide.

Rapid and sensitive determination of major polyphenolic components in Euphoria longana Lam. seeds using matrix solid-phase dispersion extraction and UHPLC with hybrid linear ion trap triple quadrupole mass spectrometry.

A rapid and sensitive method for the extraction and determination of four major polyphenolic components in Euphoria longana Lam. seeds is presented for the first time based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometry. Matrix solid-phase dispersion method was designed for the extraction of Euphoria longana seed constituents and compared with microwave-assisted extraction and ultrasonic-assisted extraction methods. An Ultra high performance liquid chromatography with hybrid triple quadrupole linear ion-trap mass spectrometry method was developed for quantitative analysis in multiple-reaction monitoring mode in negative electrospray ionization. The chromatographic separation was accomplished using an ACQUITY UPLC BEH C18 (2.1 mm × 50 mm, 1.7 µm) column with gradient elution of 0.1% aqueous formic acid and 0.1% formic acid in acetonitrile. The developed method was validated with acceptable linearity (r2 > 0.999), precision (RSD ≤ 2.22%) and recovery (RSD ≤ 2.35%). The results indicated that matrix solid-phase dispersion produced comparable extraction efficiency compared with other methods nevertheless was more convenient and time-saving with reduced requirements on sample and solvent volumes. The proposed method is rapid and sensitive in providing a promising alternative for extraction and comprehensive determination of active components for quality control of Euphoria longana products.

Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol.

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3(2) Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as Cmax, Tmax, Ke, Ka, Vd and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in Cmax (two fold, p < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.

Exploring Microstructural Changes in Structural Analogues of Ibuprofen-Hosted In Situ Gelling System and Its Influence on Pharmaceutical Performance.

The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model.

Mapping ion-induced mesophasic transformation in lyotropic in situ gelling system and its correlation with pharmaceutical performance.

PURPOSE: To investigate influence of ion induced mesophasic transformation on pharmaceutical performance of in situ gelling system consisting of glyceryl monooleate. METHODS: The prepared system showed mesophasic transformation during its conversion from sol to gel upon controlled hydration. The process of mesophasic transformation was studied by SAXS, DSC, rheology and plane polarized light microscopy. Further the influence of additives i.e. naproxen salts (sodium and potassium) and naproxen (base) on the process of mesophasic transformation was also elucidated. RESULTS: It was observed that addition of salt form of naproxen transformed W/O emulsions into cubic mesophase whereas addition of base form of naproxen formed reverse hexagonal (HII) phase upon controlled hydration. The cubic mesophase formed by naproxen salts retarded the drug release for initial 3 h whereas HII phase showed sustained drug release characteristics for naproxen base following Higuchi drug release kinetics. CONCLUSION: The current work suggests that formulations with tailor made pharmaceutical performance can be developed by selecting proper additives in the system so as to obtain the desired mesophase 'on demand' thereby controlling drug release characteristics.

Standardization and Ameliorative effect of Kalyanaka ghrita in ß-amyloid induced memory impairment in wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation. AIM OF THE STUDY: The present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration. MATERIALS AND METHODS: KG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid ß (Aß1-42). The effect of KG (oral and intranasal treatment) was evaluated through behavioral parameters such as Morris water maze, social recognition test, novel object recognition, locomotor activity, and molecular parameters, brain acetylcholinesterase, brain-derived neurotrophic factor (BDNF), inflammatory cytokines, oxidative stress markers, and antioxidants. Brain histopathology was performed for studying the architecture of the brain and plaque formation. RESULTS AND DISCUSSION: A novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aß1-42 induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. There were more marked effects with intra-nasal administration compared to oral treatment. CONCLUSION: The findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.

Fabrication, optimization and characterization of an osmotic push-pull drug delivery system for paliperidone.

Objectives: Paliperidone is a BCS class II drug with low solubility and high permeability. It has 28% absolute oral bioavailability and an elimination half-life of 23 h. An osmotic push-pull trilayer tablet currently available on the market has achieved controlled release of a low dose over an extended time period, while avoiding the need for a loading dose. However, this trilayer tablet has several disadvantages, such as complicated processing, high production costs and difficulty in achieving uniformity of the contents. Thus, the objective of this study was to overcome the above difficulties associated with paliperidone and to formulate a bilayer tablet with a similar drug profile to that of the reference listed drug Invega®. Methods: The bilayer tablets were prepared by optimization of the core and semi-permeable membrane. Effects of the curing time, and the size and number of orifices on the prepared tablets' dissolution profile were analyzed. Two different grades of polyethylene oxide were used in the core and push layer as pore formers. Results: The weight variation, friability and hardness values of the prepared tablets were well within compendium limits. The optimized bilayer parameters for the prepared tablets were curing time, 5 h; seal coat, 7% w/w; ER coat, 13% w/w; orifice size, 0.6 mm; and orifice number, 2. Further tablet formulation resulted in an F2 value of 75.67, indicating a dissolution profile similar to that of Invega®. Conclusion: Bi-layer tablets of paliperidone overcoming the drawbacks of the marketed formulation were successfully prepared, and offer advantages such as a simpler preparation process, cost effectiveness and faster preparation of the tablet core.

A Simple HPTLC Approach of Quantification of Serratol and Tirucallic Acid with Boswellic Acids in Boswellia serrata by Validated Densitometric Method with MS/MS Characterization.

This study was planned to develop a simple high-performance thin-layer chromatography method for qualitative and quantitative estimation of 3-acetyl-11-keto-ß-boswellic acid (AKBBA), ß-boswellic acid (BBA), 3-oxo-tirucallic acid (TCA) and serratol (SRT) with HPTLC-ESI-MS/MS for characterization in Boswellia serrata Roxb. oleo gum resin extract. The method was developed with hexane-ethyl acetate-toluene-chloroform-formic acid as mobile phase. RF values observed for AKBBA, BBA, TCA and SRT were 0.42, 0.39, 0.53 and 0.72, respectively. The method was validated according to International Council for Harmonisation guidelines. The concentration range for linearity was 100-500 ng/band for AKBBA and 200-700 ng/band for the other three markers with r2 > 0.99. The method resulted in good recoveries as 101.56, 100.68, 98.64 and 103.26%. The limit of detection was noticed as 25 , 37, 54 and 38 ng/band, with a limit of quantification as 76, 114, 116 and 115 ng/band, for AKBBA, BBA, TCA and SRT, respectively. The four markers were identified and confirmed in B. serrata extract using TLC-MS by indirect profiling by LC-ESI-MS/MS and were identified as terpenoids, TCA and cembranoids: AKBBA (mass/charge (m/z) = 513.00), BBA (m/z = 455.40), 3-oxo-tirucallic acid (m/z = 455.70) and SRT (m/z = 291.25), respectively.

Probing influence of mesophasic transformation on performance of self-emulsifying system: effect of ion.

Self-emulsifying systems are mixtures of oils and surfactants, ideally isotropic, sometimes including cosolvents, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastrointestinal tract. The process of self-emulsification has remained the center of attraction for most researchers. Controlled hydration of self-emulsifying systems shows formation of an intermediate gel phase which upon rupture forms an emulsion. Current work was undertaken to understand and explore the microstructural properties of intermediate gel phase which are believed to influence the performance (droplet size) of the final formulation. The effect of additives on microstructural properties of intermediate gel phase has also been investigated. Microstructural elucidation of hydrated samples of intermediate regimes was done by using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. Samples from intermediate regimes showed formation of local lamellar structure which swelled with hydration. In the present work, the effect of addition of salt form of naproxen (sodium and potassium) and naproxen (base) on microstructural properties of intermediate regimes was investigated. Systems containing naproxen salts formed larger droplets whereas naproxen base formed smaller ones. Microstructural properties of intermediate lamellar structures were well correlated with performance of the final formulation. The current studies indicate that by controlling the properties of intermediate regimes optimized formulations with desired performance can be tailor-made.

Microstructural elucidation of self-emulsifying system: effect of chemical structure.

PURPOSE: Self-emulsifying systems (SES) emulsify spontaneously to produce fine oil-in-water emulsion when introduced into aqueous phase. The self-emulsification process plays an important role during formation of emulsion. The objective of current work was to understand and explore the inner structuration of SES through controlled hydration and further to study the influence of additive on the same which ultimately governs performance of final formulation in terms of droplet size. METHODS: Droplet size of final formulations containing structural analogues of ibuprofen was determined. Microstructural properties of intermediate hydrated regimes of SES were investigated using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. RESULTS: The current work established inverse relationship between droplet size of the formulations containing structural analogues of ibuprofen and their Log P values. Microstructural analysis of intermediate hydrated regimes of the prepared samples showed formation of local lamellar structure. Structural analogues of ibuprofen significantly altered microstructure of lamellae which was well correlated with the droplet size of final formulations. In vitro drug release study showed increase in dissolution rate of lipophillic drugs when formulated as SES. CONCLUSION: The current work emphasizes the fact that tailor-made formulations can be prepared by controlling the properties of intermediate regimes.

Scaffold hopping for identification of novel D(2) antagonist based on 3D pharmacophore modelling of illoperidone analogs.

The dopamine D(2) receptor is involved in the etiology of a number of disorders, such as Parkinson's disease, Huntington's Chorea, tardive dyskinesia and schizophrenia. Antagonism of D(2) receptors is implicated in the treatment of various psychiatric disorders. In order to understand essential structural features required for D(2) antagonism, this research article elaborates on the generation of a four-point 3D pharmacophore model which was extracted from a series of 45 novel 3-[[(aryloxy)alkyl]piperidinyl]-1,2-benzisoxazole derivatives. The best pharmacophore model generated consisted of four PRRR features: a positively charged group (P), and three aromatic rings (R). Based on the model generated, a statistically valid 3D-QSAR with good predictability (Q(2) = 0.756) was derived. For the validation of the pharmacophore hypothesis, active compounds were docked against the 3D structure of the D(2) receptor which was constructed through homology modeling. Further, the derived pharmacophore was used as a query to search the Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters, such as fitness score, predicted activity and docking scores. The resulting hits present new scaffolds with a strong potential for D(2) antagonist.

Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening.

Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.

Metabolic characterization of Withania somnifera from different regions of India using NMR spectroscopy.

Withania somnifera (L.) Dun. (Solanaceae), known as Indian ginseng, is one of the most popular medicinal plants in India. Considering the importance and common use of this plant, it is necessary to investigate its holistic metabolite profile. However, with existing analytical methods which are based on TLC and HPLC­UV (or MS), it is difficult to obtain information of the whole range of compounds appropriately. In this study, the metabolic characterization of Withania somnifera leaves, stems, and roots collected in six different regions in India was performed using ¹H NMR spectroscopy followed by principal component analysis (PCA) and hierarchical clustering analysis (HCA). Of the parts of Withania somnifera analyzed in this study, the leaf was found to have the widest range of metabolites, including amino acids, flavonoids, lipids, organic acids, phenylpropanoids, and sugars, as well as the main secondary metabolites of the plant, withanolides. The ¹H NMR spectra revealed the presence of two groups of withanolides: 4-OH and 5,6-epoxy withanolides (withaferin A-like steroids) and 5- OH and 6,7-epoxy withanolides (withanolides Alike steroids). The ratio of these two withanolides was found to be a key discriminating feature of Withania somnifera leaf samples from different origins.

An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India.

INTRODUCTION: Bioequivalence is established by comparing the bioequivalence study results of generic drugs with the reference listed drug. Several global regulatory agencies have published the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. AREAS COVERED: The prime intent of the present article is to compare the regulatory guidance for bioequivalence assessment of locally acting OIDPs published by global regulatory authorities. Regulatory recommendations on bioequivalence were based on assessment for different parameters such as inhaler device, formulation, reference product selection, in-vitro, and in-vivo studies. The United States Food and Drug Administration and Health Canada suggest an aggregated weight of evidence approach and the European Medicines Agency promotes a stepwise approach, whereas though the Indian authorities have not published guidance specifically on OIDPs but provided guidelines for bioavailability and bioequivalence studies. EXPERT OPINION: For OIDPs, currently, there is no universally adopted methodology, and regulatory guidance has not been globally harmonized. By understanding and comparing bioequivalence recommendations for different regions, we can create more sensitive, and economic evaluation methods for OIDPs. This could open more alternatives of safe, effective generic OIDPs to the public.

ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model.

Beta amyloid plays a main role in the pathophysiology of Alzheimer's disease by inducing oxidative stress in the brain. Curcumin, a natural antioxidant, is known to inhibit beta amyloid and beta amyloid induced oxidative stress. However, low bioavailability and photodegradation are the major concerns for the use of curcumin. In the present study, we have formulated apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3-C-PBCA) to provide photostability and enhanced cell uptake of curcumin by targeting. Prepared nanoparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. The entrapment of curcumin inside the nanoparticles was confirmed by X-ray diffraction analysis. Physicochemical characterization confirmed the suitability of the method of preparation. The photostability of curcumin was increased significantly in nanoparticles compared to plain curcumin. In vitro cell culture study showed enhanced therapeutic efficacy of ApoE3-C-PBCA against beta amyloid induced cytotoxicity in SH-SY5Y neuroblastoma cells compared to plain curcumin solution. Beta amyloid is known to induce apoptosis in neuronal cells, therefore antiapoptotic activity of curcumin was studied using flow cytometry assays. From all the experiments, it was found that the activity of curcumin was enhanced with ApoE3-C-PBCA compared to plain curcumin solution suggesting enhanced cell uptake and a sustained drug release effect. The synergistic effect of ApoE3 and curcumin was also studied, since ApoE3 also possesses both antioxidant and antiamyloidogenic activity. It was found that ApoE3 did indeed have activity against beta amyloid induced cytotoxicity along with curcumin. Hence, ApoE3-C-PBCA offers great advantage in the treatment of beta amyloid induced cytotoxicity in Alzheimer's disease.

Regulatory Perspective of International Agencies for Development of Biosimilar Products (Monoclonal Antibodies): An Overview.

Biopharmaceutical medicines are complex molecules obtained from a living organism (plant or animal cells) and may contain components of a living organism using biotechnology. Biosimilars are closely similar to already approved biopharmaceutical products that could form a new generation of medicines that are available widely at an affordable cost. The expiry of patent and data protection of Remicade (infliximab) aggravated biosimilar acceptance in the open market. Analysis of data package submitted for infliximab biosimilar and assessment reports published by agencies shows the importance of European Medicines Agency (EMA) product-specific guidelines (monoclonal antibodies) that are being followed by different regulatory agencies worldwide. Considering utilization of case-by-case basis for biosimilar development, infliximab biosimilar product evaluation assessment report suggests similarity in nature and extent of data required in analytical, nonclinical, and clinical studies even on utilizing cell lines different from the reference product's. Specific additional clinical study (phase III) is required for a biosimilar to be authorized by the Ministry of Health, Labour and Welfare (MHLW). US Food and Drug Administration and EMA widely accept the concept of extrapolation to other indications approved for the reference product. However, the Ministry of Health, Labour andWelfare, Japan shows a conservative approach for extrapolation to other indications in the absence of direct or indirect safety and efficacy data.

An Overview of the Drug Registration Requirements for Export to Tanzania, Nepal, and Cambodia.

In the semiregulated market, different countries have varying requirements of registration for export to such a specific country or region. The objective of the present study is to give a comparative overview of pharmaceutical registration requirements for export to Tanzania, Nepal, and Cambodia. In the African region especially, east Africa including Tanzania is an emerging market for pharmaceuticals. The Tanzania Food and Drugs Authority is the drug regulatory body in Tanzania and it follows the Common Technical Document (CTD) format for dossier submission. However, Nepal is still a developing country with respect to the pharmaceutical sector. The drug governing body in Nepal, Department of Drug Administration, has its own nation-specific guidelines for drug regulation, but the CTD format is also acceptable for dossier submission. In Cambodia, the Department of Drugs and Food is the drug regulatory authority that comes under the Ministry of Health of Cambodia. As Cambodia is included in the Association of Southeast Asian Nations (ASEAN) body, it follows the ASEAN CTD (ACTD) format for dossier submission.

Development of stability-indicating HPLC method and accelerated stability studies for osmotic and pulsatile tablet formulations of Clopidogrel Bisulfate.

The purpose of the present study is to develop a simple, rapid and sensitive stability-indicating high-performance liquid chromatography (HPLC) method for Clopidogrel Bisulfate (CBS) and further extending it for assessment of CBS stability in osmotic and pulsatile tablet formulations tested under accelerated conditions. A stability-indicating HPLC method for quantitative determination of CBS in gastro-retentive formulations is developed by using a C18 HPLC column, acetonitrile and 0.1% formic acid (60:40 v/v) as mobile phase, with a flow rate of 0.9 mL/min, UV detection at 222 nm and subsequently validated. The key objective was to analyze the stability profile of formulations under accelerated conditions. The retention time (Rt) of CBS was observed as 5.9 min with the linearity range between 0.06-1.95 µg/mL. Forced degradation studies were performed on bulk samples of CBS using acidic, basic, oxidative, thermal (80 °C) and photolytic (under sunlight) conditions. The resulting method was validated as per ICH Q2(R1) guidelines. Moreover, an attempt has been made to identify the degradation products by Liquid chromatography-mass spectrometry (LC-MS) analysis. The proposed method was successfully applied to novel gastro-retentive tablet formulations (osmotic tablet and pulsatile tablet) for assessment of stability under accelerated conditions.

Application of ion exchange resin in floating drug delivery system.

The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.