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

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

EXPLORING PROPERTIES OF SWEET BASIL SEED MUCILAGE IN DEVELOPMENT OF PHARMACEUTICAL SUSPENSIONS AND SURFACTANT-FREE STABLE EMULSIONS

Objective: The objective of the investigation was to isolate mucilage from sweet basil seeds and explore its physicochemical properties for the development of pharmaceutical suspensions and surfactant-free stable emulsions.Methods: Possible applications of sweet basil seed mucilage in the pharmaceutical field for dosage form development are being explored. The physicochemical and functional properties of the mucilage from the seeds of the Ocimum basilicum L. (Sweet basil) have been investigated for stabilization of suspensions and emulsions. The following analyses were performed: FTIR spectroscopy, phytochemical tests, XRD, swelling and rheological studies.Results: The analyses showed that the mucilage is rich in glucose, mannose, and xylose. High swelling index values varying from 100±10 to 200±13%, high water-holding capacity of 97.5±2.4 g/g mucilage and reasonable oil holding capacity of the mucilage (13.2±1.3 g/g mucilage) makes it an ideal candidate for utilization as viscosifier and stabilizer of suspensions and surfactant-free emulsions. Adult and paediatric paracetamol suspension formulations with 1%w/v mucilage have exhibited flocculated nature and good stability owing to its high sedimentation volume(F= 0.85-0.98) and good redispersibility. Sunflower oil emulsions prepared with 0.25%w/v mucilage demonstrated emulsion stability index of 105.714 on 5th day and extremely low creaming rate of 0.0004 cm/h thus confirming maximum stability compared to emulsions developed with 0.3-0.5% w/v mucilage.Conclusion: The mucilage isolated from Ocimum basilicum L. seeds may be regarded as a functional biomaterial for pharmaceutical use to ensure quality and stability of liquid dosage forms

Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor

Background: BQCA is a selective allosteric modulator of the M1 mAChR. Results: Residues that govern BQCA activity were identified using mutagenesis and molecular modelling. Conclusion: BQCA likely occupies a pocket overlapping prototypical mAChR modulators and gains selectivity through coop- erativity with orthosteric ligands. Significance: Understanding the structural basis of BQCA function can provide insight into the design of more tailored allosteric ligands

Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor

Established therapy in Alzheimer’s disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M1 muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pKB), intrinsic efficacy (τB), and both binding (α) and functional (β) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action

Allosteric interactions at adenosine A1 and A3 receptors: new insights into the role of small molecules and receptor dimerization

Keywords:adenosine;allosterism;receptor;GPCR;dimerization;biased signalling The purine nucleoside adenosine is present in all cells in tightly regulated concentrations. It is released under a variety of physiological and pathophysiological conditions to facilitate protection and regeneration of tissues. Adenosine acts via specific GPCRs to either stimulate cyclic AMP formation, as exemplified by Gs-protein-coupled adenosine receptors (A2A and A2B), or inhibit AC activity, in the case of Gi/o-coupled adenosine receptors (A1 and A3). Recent advances in our understanding of GPCR structure have provided insights into the conformational changes that occur during receptor activation following binding of agonists to orthosteric (i.e. at the same binding site as an endogenous modulator) and allosteric regulators to allosteric sites (i.e. at a site that is topographically distinct from the endogenous modulator). Binding of drugs to allosteric sites may lead to changes in affinity or efficacy, and affords considerable potential for increased selectivity in new drug development. Herein, we provide an overview of the properties of selective allosteric regulators of the adenosine A1 and A3 receptors, focusing on the impact of receptor dimerization, mechanistic approaches to single-cell ligand-binding kinetics and the effects of A1- and A3-receptor allosteric modulators on in vivo pharmacology

Electro-Quasistatic Animal Body Communication for Untethered Rodent Biopotential Recording

Continuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation >99% when compared to traditional wireless communication modalities, with a 50× reduction in power consumption