Sanjay

The present investigation deals with the formulation of mouth dissolving oral films of Rizatriptan which is used for the treatment of migraine. Rapidly dissolving films have acquired great importance in present scenario because of exclusive properties. The films of Rizatriptan were carried out using different grades of HPMCE3, E6, and E15, maltodextrin DE6, xanthan gum and other polymers by solvent casting method.  The prepared films were evaluated for film thickness, folding Endurance, Surface pH, morphological properties, %drug content and content uniformity, tensile strength, percent elongation, in vitro disintegration time and in vitro dissolution studies. The optimized formulation F24 prepared using HPMC E15 showed minimum disintegration time (9 sec), highest dissolution rate i.e. 99.6% of drug within 8 min and satisfactory physicochemical properties. The optimized film was evaluated for its bioavailability compared with pure drug as reference standard. Statistical analysis declare that no significant difference between the bioavailability parameters Cmax, Tmax, AUC0–∞ and AUC0–t of the test film (F24) and the reference product (Pure drug) indicated that they exhibited comparable plasma level-time profiles. These results revealed that the mouth dissolving film containing Rizatriptan is considered to be effectively useful for the treatment of migraine where quick onset of action is expected.

Lyophilization is promising approach to increase the shelf life of liposome. The major limitation in the widespread use of liposome is its instability. The aim of this study was to investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties Lyophilization is used to ensure an increased shelf life of liposomes by preserving them in dry state more stable than the aqueous dispersion. When stored as aqueous system the encapsulated drugs are released & the liposome might aggregate or fuse. The process of lyophilization without cryoprotectant resulted in particle size increased & significant content leakage. This review work suggests that the investigation of stability of lyophilized liposomes containing PC (Phosphatidyl Choline) & cholesterol. Liposomes sphere-shaped vesicles consisting of one or more phospholipids bilayer in which both hydrophilic & hydrophobic drug entity can be incorporated. Due to their size & hydrophobic & hydrophilic character liposomes are promising for drug delivery. This structure turns liposomes into ideal drug carriers, since hydrophilic drugs tend to entrapped in the core; while hydrophobic ones will be entrapped within the lipid bilayers. Liposome is one of the most successful drug delivery system applying nanotechnology to potentiate the therapeutic efficacy & reduce toxicities of conventional medicines. The encapsulation efficiency partially depends upon the logP of drug. Lyophilization is a strategy often employed to improve liposomal formulation stability, due to reactivity being far less pronounced in the solid versus aqueous state.

Last three decades enormous work has been carried out on computational chemistry. The projects given for discovery of New Chemical Entities by these methods and gets a safe, potent drug molecule. However, the commercial output for the pharmaceutical company with these methodologies is negligible. Most of the drugs discovered in medicinal chemistry are accidentally. Thus synthesis of focused compound libraries and their pharmacological screening by efficient methods becomes powerful tool for drug discovery. But some additional points are required to move towards aryloxypropanolamines As 1-Aryloxy-3-(N4-substituted piperazinyl) propan-2 OLS (aryloxypropanolamines) shows β-adrenergic receptor antagonist activity (β-blockers), these chemical entities are applicable in management of various diseases due to their therapeutic effects. The main clinical indications of β-blockers are in the area of cardiovascular diseases, such as hypertension, angina pectoris, myocardial infarction and cardiac arrhythmias1-4. However, some β-blockers readily access the brain because of their lipophilicity and can influence some central nervous system functions. Therefore, Propranolol has been used for the treatment of anxiety syndromes, prophylaxis of migraine headaches, schizophrenia, alcohol withdrawals and tremors5-8. Looking at the biological profile of various aryloxypropanolamines (also Enciprazine) molecule, synthesis of various derivatives of Enciprazine having different aryloxy moiety and amine moiety (by taking different N- alkyl/aryl substituted piperazine) was planned to get safe, potent or new activity molecules.

Last few decades, research data has prompted a passionate debate as to whether oxidation, or specifically, oxidative stress mediated by free radicals/reactive oxygen species (ROS)/reactive nitrogen species (RNS), is a primary or secondary cause of many chronic diseases. Lagenaria siceraria is fair source of ascorbic acid, beta carotene and different phytochemicals to heal many disorders. It shows ribonucleolytic, antihyperlipidemic, hepatoprotective, antioxidant, immunomodulatory, cardiotonic activity. The collection and identification of juice of Lgenaria siceraria and preparation of four fractions of concentrated juice were carried out and preliminary phytochemical and pharmacological screening of same fractions was done. Preliminary pharmacological screening of each fraction was investigated to find out desired in-vitro antioxidant activity. Aqueous fraction showed better yield because of polarity of compound. Preliminary phytochemical screening of four different fractions had various phytochemicals like steroids, flavonids, glycosides, saponins, etc. As we had followed the biological activity guided isolation of active constituents, the fractions were evaluated for antioxidant activity. Isolated aliphatic and saponins moiety may be responsible for the antioxidant activity.

A   mixture  of  acamprosate calcium, disulfiram and ondansetron hydrochloride   is used for the   treatment of   drug abuse including alcoholism. In this study, a UV- spectrophotometric method was proposed for simultaneous determination of acamprosate calcium, disulfiram and ondansetron hydrochloride.  Determination of these drugs was performed using the 1D value of acamprosate calcium at 207 nm, 2D value of disulfiram at 270 nm and 3D value of ondansetron hydrochloride at 310 nm. The  analysis  method  was validated for various parameters according to ICH guideline and linear  over  the  range  of  8-48,4-24, and  2-12  µg ml-1 for acamprosate calcium,   disulfiram  and ondansetron hydrochloride, respectively.  The correlation coefficient was found to be 0.998, 0.998 and 0.999 for ACM, DIS and OND respectively. Within-day and between-day precision and accuracy values for all three compounds were within an acceptable range .The developed method was used for simultaneous determination of these drugs in pharmaceutical individual dosage forms and in laboratory mixture no interference from excipients was observed.

Development of amphiphilic drug-lipid complexes is a potential approach for improving delivery of the drugs by increasing solubility, release profile and oral bioavailability. Rutin, a polyphenolic flavonoid, shows several biological effects like capillary protectant, anti-oxidant, anti-inflammatory, anti-aging, cardio-protective, anti-thrombotic and neuroprotective, but its use is limited due to its low aqueous solubility. To overcome this limitation, phospholipid complex of Rutin was developed to improve its aqueous solubility for better absorption through the gastrointestinal tract and this might result in improved bioavailability. The Rutin phytosomes prepared by solvent evaporation method using different ratios of Rutin and Soybean phosphatidylcholine (1:1, 1:2 and 1:3) was evaluated for percentage yield, compatibility studies by infra-red spectroscopy, particle size, poly dispersity index, zeta potential, drug content and were found to be within the acceptable range. Surface morphology by scanning electron microscopy, solubility studies, in-vitro drug release and stability studies also were carried out. The phospholipid complex of Rutin was found to be fluffy and porous with rough surface. The water solubility of Rutin was improved from 0.058mg/ml to 0.475 mg/ml in the prepared Phytosomes. The in-vitro drug release studies showed that there is no drug release from pure drug and F1 formulation up to 120min in acidic buffer pH 1.2; while in phosphate buffer pH 7.4 showed releases about 49.3% and 92.85% respectively, which indicates the significant enhancement of dissolution of Rutin phytosomes compared to pure drug. Stability studies suggested that the formulations were stable. In this study, Phytosomes could be successfully tailored for Rutin with improved dissolution characteristics which is promising for lowering the influence of exogenous factors and increasing drug delivery.

A novel polymer based on azobenzene-4,4’-diacetic allyl ester as core linker polycondensated with methyl methacrylate and n-butyl methacrylate was conveniently synthesized for the purpose of targeting colonic drug delivery. The cross linker was characterized by infrared spectroscopy, nuclear magnetic resonance and mass spectroscopy. The synthesized polymers (PMB) showed good film forming. Comparative study of synthesized polymers was done using In-vitro drug release pattern of budesonide from polymer coated capsule formulation in colonic media. Budesonide capsules coated with PMB1:1:2: B and PMB1:1:3: B showed maximum drug release in colon in a sustained release manner.

Gastro retentive systems can remain in the gastric region for several hours and hence prolongs the gastric residence time of drugs and improve the bioavailability. The aim of this project was to develop sustained release floating matrix tablet for hydroalcoholic extract of neem leaves using psyllium husk as release controlling polymer along with synthetic polymer HPMC K100 M and sodium bicarbonate as gas generating agent. The tablets were prepared by direct compression method. Seven different formulations A1 to A7 were prepared by varying the concentration of psyllium husk, HPMC K100 M and sodium bicarbonate. Tablets were evaluated for pre and post compression parameters like tablet thickness, hardness, weight variation, drug content, friability, floating lag time and in vitro drug release. Results for angle repose, swelling index, weight variation, drug content, thickness, hardness, % friability for all the formulations were found to be in acceptable limit. In vitro drug release was observed for 12 hours and all the tablet formulations followed zero-order kinetics and/ or Korsemeyer-Peppas model in drug release. The formulations were optimized on the basis of buoyancy time and in vitro drug release. The optimized formulation was found to be A4 with 98.77% in vitro drug release in 12 h and 212 seconds buoyancy time. The BaSO4 tagged formulation, similar to formulation A4 was tested in in vivo gastric retention study in rabbits. It was observed that formulation kept floating in the stomach region till 10 hours. Formulations containing combination of psyllium husk and HPMC K100M with sodium bicarbonate as gas generating agent can be a promising way for formulating gastroretentive drug delivery systems.

The synthesis of Nitrogen containing heterocycles particularly substituted pyrrolidines constitutes very important moieties of many biologically active molecules1 including natural and non-natural substances. The synthesis of functionalized pyrrolidines continues to attract interest, both for their synthetic challenges,2 and also their value in synthetic chemistry3 and their diverse biological properties.4 The present work includes the synthesis of substituted pyrrolidines from alkyl dihalide and primary amines by simple and efficient cyclocondensation process. This methodology gives varies of substitution pattern on 2,3-position of the pyrrolidines5 Scheme 1. This strategy improved greener synthetic methodology and worked out as a simple and straightforward one-pot approach for the synthesis nitrogen containing heterocycle as pyrrolidines.

Self nanoemulsifying drug delivery (SNEDDS) is used for drugs which exhibit low water solubility. Dissolution is the rate limiting factor for these drugs. SNEDDS are capable of improving the bioavailability substantially of such drugs. They are formulated by utilizing an oil phase, surfactant and a co-surfactant. This formulation forms nano emulsion (O/W type) on contact with aqueous body fluids i.e. gastric juices when administered orally. Solid SNEDDS (s- SNEDDS) can also be formulated in the form of tablet which shows greater advantages. With recent and potential future developments, this technology will continue to enable novel applications in drug delivery and overcome limitations associated with the delivery of poorly water soluble drugs, mainly those belonging to BCS class-II and class-IV.