EFFECT OF CELLULOSIC POLYMER ON PHYSICO MECHANICAL PROPERTIES OF SUPERPOROUS HYDROGEL OF AN ANTIHYPERTENSIVE DRUG AND DRUG RELEASE KINETICS FROM IT

Objective: Super porous hydrogels (SPHs), a novel drug delivery system can be developed to retain drugs in the gastric medium. The aim of the present investigation was to prepare superporous hydrogels (SPHs) of Atenolol to release the drug in sustained manner in the gastric environment and study the effect of two grades of hydroxyl methyl cellulose along with Carbopol 971p on the physico mechanical properties and drug release kinetics of the formulations. Methods: Superporous hydrogels of Atenolol were prepared with two grades of Hydroxy Propyl Methyl Cellulose (HPMC K100M and HPMC K15 M) along with Carbopol 971p the structural morphology of hydrogel was observed by Scanning Electron Microscopy. Study on Physico mechanical characteristics and drug release were done. Results: Scanning Electron microscopy studies of the formulations revealed the presence of large number of pores in different size ranges like 1 µm, 2 µm, 10 µm, confirming the formulations as superporous hydrogel. A correlation had been found between porosity, density and % swelling index. The drug release data from the formulations obeyed Higuchi and Korsmeyer-Peppas kinetics. Further, the data were fitted to the Kopcha model for confirming drug release by a combination of diffusion-controlled and chain relaxation–swelling mechanism. Conclusion: Among the six formulations, where HPMC K15 M and HPMC K100 M both were present, the gel became more hydrophobic and retarded the release of drug. From the drug release kinetics data, it can be concluded that the diffusion mechanism predominated the drug release process, leading to quasi diffusion and Fickian diffusion mechanism

OLEOGELS OF OLIVE OIL AND SOYBEAN OIL FOR TOPICAL DRUG DELIVERY: A COMPARATIVE ANALYSIS

Objective: The objective of the present investigation was to develop olive and soybean oil-based oleogels with Span 40 and/or Tween 80 (as gelator and/or surfactant) and determine the critical gelator concentration (CGC), characterise and compare the rheological, thermal properties and drug release profile of the gels formed for topical delivery. Methods: Olive and soybean oil-based Span 40 and Span 40/Tween 80 oleogel formulations were prepared by solid fiber mechanism and subjected to organoleptic evaluation, FT-IR spectroscopy, thermal analysis, rheological study, kinetic modeling of gelation and drug release. Results: The critical gelator (Span 40) concentration was found to be lower for olive oil (12% w/v) and depend on the type of oil. Tween 80 reduced CGC of soybean oleogels only. Soybean oil-based oleogel containing 18% w/v Span 40 was found to form more flexible, less viscous and thermally less stable formulation with better release of paracetamol as evident from lower melt flow index, Tg value, lower β and higher α value compared to olive oil-based oleogel with 12% w/v Span 40 (CGC). Surfactant addition can be assumed to modify the microarchitecture of the oleogels to a great extent to produce more flexible and thermally stable gels with even better drug release profile. Span-Tween based soybean oleogel formed a gel-matrix whereas matrix in olive oil-based oleogels containing Span only became slightly flexible to release the drug in zero-order fashion on the addition of surfactant cogelator. Conclusion: Nature of oil exerts profound influence on the rheological, thermal and release profile of oleogels containing Span 40 as gelator and/or Tween 80 as surfactant cogelator

FORMULATION AND IN VITRO CHARACTERISATION OF SOYBEAN OIL-HPMCK4M BASED BIGEL MATRIX FOR TOPICAL DRUG DELIVERY

Objective: Hydrogels with scope for utilization in numerous fields possess limited applications due to problems in incorporating wide range of drugs and crossing the lipophilic barrier of the skin. Attempts to overcome these problems by developing organogel hold drawbacks. Challenges posed by drug lipophilicity or skin permeation can be solved by developing bigel formed via combination of lipophilic and hydrophilic gel phases in a definite proportion. The objective of the present study is to formulate and characterize matrix type bigel of soybean oil and HPMCK4M for topical drug delivery. Methods: Four batches of bigels were developed with two organogel formulations of soybean oil containing 20 and 22% w/v Span 60. Both organogels and bigels were examined for compatibility by FTIR spectroscopy, hemocompatibility and characterized for physical appearance, pH, rheological behavior and in vitro drug release pattern. Results: FTIR study confirmed compatibility between paracetamol and components of organogel or bigel. The oily feel of organogels disappeared with bigels which possessed a creamy and smooth texture. Pseudoplastic behaviour was confirmed by Ostwald-de wale power-law model in both organogels and bigels. Improved drug release was observed in bigel (BG1) formulation containing 3%w/v HPMCK4M and soybean oil based organogel with 20% w/v Span 60 as compared to the corresponding organogel (OG1). Organogels were foundto follow either zero-order kinetics (OG1) or Korsmeyer-Peppasmodel (OG2) while the formation of matrix was exhibited in bigels with drug diffusion predominantly of non-Fickian type. Conclusion: Therefore, bigels of soybean oil based organogel with HPMCK4M hydrogel formed gel matrix demonstrating improved drug release for topical application compared to organogel

HPMC AS CAPSULE SHELL MATERIAL: PHYSICOCHEMICAL, PHARMACEUTICAL AND BIOPHARMACEUTICAL PROPERTIES

The most common instability problem of gelatin capsules arises from negative impact of extremes of temperature and especially atmospheric relative humidity on the mechanical integrity of the capsule shells with adverse effect extended even to the fill material. Moreover, choice of fill materials is highly restricted either due to their specific chemical structure, physical state or hygroscopicity. Additional reports of unpredictable disintegration and dissolution of filled hard gelatin capsules in experimental studies have prompted the search for a better alternative capsule shell material. The present review aims to provide an overview on the physicochemical, pharmaceutical and biopharmaceutical properties of hydroxypropyl methylcellulose (HPMC) as capsule shell material and perform comparative evaluation of HPMC and gelatin in terms of in vitro/in vivo performance and storage stability. HPMC capsule provides a highly flexible and widely acceptable platform capable of solving numerous challenges currently facing the pharmaceutical and nutraceutical industries and expands the possibilities for selection of different types of fill materials. The current topic introduces a new section on influence of various factors on in vitro dissolution of HPMC capsules. Delayed in vitro disintegration/dissolution of HPMC capsules in aqueous medium does not produce any negative effect in vivo. However, advancements in the processes of production and filling of HPMC capsule shells and detailed studies on effects of various parameters on their in vitro/in vivo dissolution would establish their supremacy over hard gelatin capsules in future

DEVELOPMENT AND CHARACTERIZATION OF ORAL SWELLABLE RAPID RELEASE FILM WITH SUPERDISINTEGRANT-SURFACTANT

Objective: Oral disintegrating films consisting of hydrophilic polymer are designed to be quickly hydrated by saliva, adhere to the mucosa and disintegrate rapidly to release the drug. The aim of the present study was to prepare stable, flexible swellable rapid release oral films with hydroxypropyl methylcellulose E15 LV (HPMC) and polyvinyl alcohol (PVA) in different ratios. Guar gum was incorporated as the mucoadhesive agent. In order to achieve rapid disintegration of the film cross carmellose sodium (superdisintegrant) and surfactant like Tween 80 were added. The model drug used in the study was diclofenac sodium. Methods: Films were developed using HPMC E15 LV and PVA by solvent casting method and characterized for thickness, swelling index, disintegration time, folding endurance, drug content, and in vitro drug release pattern and kinetics. Results: The prepared swellable rapid release oral films were quite flexible and transparent with a smooth texture. The swelling index study confirmed that the films possessed the desired swelling property. Fastest disintegration was observed with the oral film containing HPMC: PVA in the ratio of 2:1, guar gum at 120 mg, 20% w/w crosscarmellose sodium and 4%w/w Tween 80. The swellable rapid release oral films were found to follow either Higuchi or Korsmeyer-Peppas model with drug release following either Fickian or non-Fickian diffusion. Maximum drug release of around 70% was observed from the above-mentioned film in 1hr in simulated salivary fluid. Conclusion: Therefore, swellable rapid release oral films with HPMC E15 LV: PVA, guar gum, croscarmellose sodium and Tween 80 demonstrated satisfactory swelling, rapid disintegration and improved drug release for oromucosal absorption

DESIGN OF DISSOLUTION STUDY PROTOCOL FOR PULMONARY DOSAGE FORMS: CRITERIA FOR SELECTION OF BIO-RELEVANT DISSOLUTION MEDIUM

Pulmonary dosage forms constitute an important route of drug delivery for systemic absorption of drugs in management of respiratory diseases as well as diseases such as diabetes, migraine, osteoporosis, and cancer. Performance of different pulmonary dosage forms is greatly influenced by aerodynamic particle size distribution of inhalable particles, spray pattern, fraction of dose actually deposited on pulmonary epithelium, dissolution of active pharmaceutical ingredient and ultimately absorption across pulmonary barriers. In vitro dissolution study should be designed to predict in vivo performance precisely, providing key information on bioavailability and establishing in vitro-in vivo correlation. To obtain meaningful data from dissolution study, focus should be on composition of dissolution medium, dissolution conditions and dissolution test apparatus. For pulmonary dosage forms, selection of physiologically relevant dissolution medium, mimicking lung fluid (LF) is a challenging task. Attempts are being made to develop bio-relevant dissolution medium to overcome the limitations associated with use of conventional media lacking lung surfactant proteins, or several salts normally present in pleural fluid. Use of simulated LFs can give a better understanding of the release mechanisms and possible in vivo behavior of pulmonary dosage forms thereby enhancing the predictive capability of the dissolution testing. In the review, efforts have been taken to provide comprehensive information on composition, physicochemical characteristics and functions of physiological LF, challenges associated with the design and development of dissolution study protocol for pulmonary dosage forms, criteria for selection of an appropriate bio-relevant dissolution medium, comparative study on various reported bio-relevant dissolution media and dissolution apparatuses employed for in vitro characterization of performance of pulmonary dosage forms

PHYSICOCHEMICAL AND PHARMACEUTICAL CHARACTERISATION OF MUCILAGE FROM SWEET BASIL SEED

Objective: Gums and mucilages are of immense significance as excipients owing to their renewable natural sources, cheapness, ready availability, biodegradability, non-toxicity, ability to undergo hydration and swelling rapidly. To satisfy the ever-increasing demand for highly specific and functional excipients, sweet basil (Ocimum basilicum L.) has been selected for the purpose of isolation of mucilage from its seeds and its physicochemical and pharmaceutical characterisation. Methods: Physicochemical characterisation of sweet basil seed mucilage was carried out by FTIR spectroscopy, HPTLC, phytochemical tests, X-ray diffractometry, studies on mucilage hydration, water holding capacity and swelling behaviour. Determination of compressibility index, Hausner ratio and angle of repose was done as part of pharmaceutical characterisation of mucilage. Results: The geometric diameter, sphericity and surface area of the seed have been found to be 1.24±0.31 mm, 0.62±0.01 and 4.83±0.5 mm2 respectively. From microscopy, mucilage from seeds was seen to emerge as spiral filaments as soon as they were placed in water. The FTIR study reveals the mucilage to be a carbohydrate containing–OH groups with intermolecular hydrogen bonding as in polysaccharides, with 1→4 glycosidic bonds. Qualitative phytochemical screening of Ocimum basilicum L. seed mucilage (BSM) revealed the presence of non-reducing sugars, gums and mucilage. X-ray diffractogram presented its amorphous structure. The HPTLC profiles of BSM in n-butanol: acetic acid: water (4:1:1) at 254 nm and at 366 nm (before and after spraying with p-anisidine) revealed several bands with Rf values ranging from<0.1 to 0.5. The water-holding capacity of the mucilage has been found to be 97.5±2.4 g/g mucilage and swelling index values (0.1-0.5% w/v) were in the range of 100±10 to 200±13 at 25 °C. BSM was found to possess fair to passable flow property with Hausner’s ratio of 1.247 and angle of repose of 37.57°. Conclusion: Therefore, mucilage from sweet basil seed can be employed as an excipient in manufacture of tablets by wet granulation after addition of suitable lubricants and also in development of liquid dosage forms

THERAPEUTIC POTENTIAL OF PLANT-DERIVED OLIGOSTILBENES AND STILBENE GLYCOSIDES

Stilbenoids constitute a major class of plant-derived secondary metabolites occurring in abundance across several families and are well-known for their nutritional and health-promoting benefits. Several investigations have established their therapeutic potential in the management of different types of cancer, neuroinflammation, arthritis, disorders in lipid metabolism, microbial infection etc. Studies on resveratrol monomer, oxyresveratrol, their synthetic analogs, piceatannol, pterostilbene can be found in the literature. But a collective and comprehensive review on chemistry, pharmacological effects, structure-activity relationship and pharmacokinetics of plant-derived oligostilbenes and stilbene glycosides is missing. These phytochemicals are generally characterised by poor oral bioavailability due to extensive first-pass metabolism and conjugation. The present chapter aims to fill up these lacunae and also focuses on further studies that can be performed in the future to translate these immensely potential secondary metabolites into human clinical setting from cell culture and animal studies at the preclinical level for effective therapeutic intervention of various pathological conditions