Pharmaceutics

The present study was undertaken to investigate the effect of standardized aqueous extract of Picrorhiza kurroa Royle ex Benth. on diabetes. Diabetes mellitus was induced with streptozotocinnicotinamide and rats found diabetic were orally administered standardized aqueous extract of Picrorhiza kurroa (100 and 200 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) or vehicle (0.3% carboxy methyl cellulose suspension) for 14 days. Fasting blood glucose levels and lipid profiles were measured in control as well as diabetic rats after two week treatment. In addition, liver glycogen level of Picrorhiza kurroa extract (PkE) treated diabetic rats were compared to that of control and diabetic control rats. Oral glucose tolerance test was also performed on nondiabetic normal rats. Statistical analyses were performed by one way analysis of variance followed by Tukey-Kramer multiple comparisons test. PkE treatment induced significant reduction (p < 0.001) in elevated fasting blood glucose level in streptozotocinnicotinamide induced type-2 diabetic rats. In oral glucose tolerance test, oral administration of PkE increased the glucose tolerance. PkE treatment also significantly (p < 0.001) reversed the weight loss associated with streptozotocin treatment. These findings provide in vivo evidence that standardized extract of Picrorhiza kurroa possess significant antidiabetic activity in streptozotocin-nicotinamide induced type-2 diabetes mellitus in rats.

Recent studies have revealed diverse therapeutically interesting pharmacological properties of a standardized Hypericum perforatum extract (HpE) potentially useful for treatments of patients with metabolic and psychiatric disorders. Consequently, the presented experiments were designed to test usefulness of the extract for the treatment of comorbid conditions of mood disturbances and anxiety in diabetic rats. Type 2 diabetes mellitus was induced in overnight fasted rats by a single i.p. injection of streptozotocin (STZ; 65 mg/kg), 15 min after an i.p. injection of nicotinamide (120 mg/kg). HpE was administered orally (100 and 200 mg/kg b.w..) to diabetic animals for 14 days. Anxiolytic activity was evaluated using open-field exploration test (OFT) and elevated plus maze (EPM) test. Antidepressant activity was assessed using Porsoltís forced swim test (FST). Fasting blood glucose levels in different groups were analyzed on the 14 th day. Diabetic rats showed significant increase in anxiety in OFT and EPM compared to non diabetic normal control rats. Diabetic rats treated with HpE have shown significant anxiolytic activity in OFT and EPM test. In FST, immobility period of vehicle treated diabetic rats was significantly increased (p < 0.05) compared to normal control rats. Treatment with HpE significantly decreased (p < 0.001) immobility period compared to vehicle treated diabetic control rats. HpE treatment significantly reduced elevated blood glucose levels in diabetic rats. The presented observations strongly suggest that HpE could be suitable alternative therapeutic option for prevention, as well as treatment, of comorbidities caused by, or associated with, depression, anxiety and diabetes.

Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity.

"""Excipients are the integral part of pharmaceutical products development to achieve desired product profile(stability and efcacy). This review deals with understanding of the physicochemical properties of excipients used
in parenteral formulation development for solution, suspension and lyophilized drug products. However, in spite of proper excipients selection, judicious use during formulation manufacturing process based on their critical properties is also important to avoid negative effects such as loss of drug solubility, activity and stability. This paper deals with proper selection of excipients in lyophilized drug products which gives high critical temperature, good bulking properties avoiding melt back and collapse with improved dried product appearance. We have also emphasized on appropriate selection of excipients for solution, suspension injectable dosage forms and linking their physiochemical properties with optimum manufacturing method with suitable case studies. This review will highlight various excipient related issues optimizing product performance with documented references and practical approaches based on scientific justification. The reader will gain better understanding of excipients complexity during stability studies and resolving problems with practical approach."

Excipients are typically the major components in a drug product. Many formulations contain only a small percentage of the active drug molecules. Pharmaceutical excipients or additives are compounds added to the inished drug products to serve a speciic function. They are added to increase bulk, aid manufacturing, improve stability, enhance drug delivery and targeting, and modify drug safety or pharmacokinetic proile. Ingredients that are used during drug product manufacturing but may not be present in the inished drug product are also considered excipients (examples include water for lyophilized products, and inert gases in the head space of containers) (1). In recent years the "functionality" of excipients in a dosage form (similar to pharmacological activity of an active pharmaceutical ingredient or drug substance) has been recognized by USP & European Pharmacopoeia. Many excipient monographs do not address this aspect of excipient functionality or its control. Excipients are traditionally referred to as inactive or inert ingredients to distinguish them from active pharmaceutical ingredients. Excipients may not be as inert as the term inactive suggests. Due to safety issues, several countries have restrictions on the type or amount of excipient that can be included in the formulation of parenteral drug product. For example, in Japan, the U.S., and the E.U., amino mercuric chloride or thiomersal use is prohibited, despite the presence of these excipients in products in other regions (2). Excipients are the integral part of pharmaceutical products development to achieve desired product proile (stability and eficacy). This review deals with understanding of the physicochemical properties of excipients used in parenteral formulation development for solution, suspension and lyophilized drug products. However, inspite of proper excipients selection, judicious use during formulation manufacturing process based on their critical properties is also important to avoid negative effects such as loss of drug solubility, activity and stability. This paper deals with proper selection of excipients in lyophilized drug products which gives high critical temperature, good bulking properties avoiding melt back and collapse with improved dried product appearance. We have also emphasized on appropriate selection of excipients for solution, suspension injectable dosage forms and linking their physiochemical properties with optimum manufacturing method with suitable case studies. This review will highlight various excipient related issues optimizing product performance with documented references and practical approaches based on scientiic justiication. The reader will gain better understanding of excipients complexity during stability studies and resolving problems with practical approach.

Medicated chewing gum has a history for about a century. Now-a-days it is considered to be a potential and convenient modified release drug delivery system which can be used in pain relief medication, smoking cessation, travel illness, freshening of breath, prevention of dental caries, alleviation of xerostomia, vitamin or mineral supplementation etc. Medicated chewing gums are prepared by using a water insoluble gum base with water soluble bulk portion. This formulation offers both local and systemic effects and has a range of advantages over conventional oral solid dosage forms. USP currently has no in vitro release testing apparatus for the evaluation and determination of drug release from the prepared chewing gums. But European Pharmacopoeia adopted a compendial apparatus to do so. Medicated chewing has drawn attention to the researchers as potential drug delivery system and it could be a commercial success in near future.

A virus that was detected somewhere in Africa had swept the world off its feet via internet. Now as we ponder over which of the two, Ebola or E-communication, is more panic-causing, clinical researchers have found short term solutions to the viral outbreak. Troll community found other ways to keep people LOL-ing over the virus. Sadly, this troll-virus has been found to more widespread than the disease itself. Strange are the ways of this world. Despite strict measures by governments across the globe to contain the disease, the sly virus makes it to every continent. Symptoms of the viral infection might show up in 2 days but the rage over the internet did not take more than a day to spread. Fever, sore throat, muscle pain and headache were common symptoms in both, Ebola patients and E-bola patients. Some even began to bleed internally. Now since the disease is a contagious one with the potential of spreading across countries, few politicos banked on conspiracy theories such as it being a biological weapon, not knowing that the virus had been identified as early as 1976. It is believed, of course based on sound experiment-based reasoning, that the virus made its way by afflicted animals. However there is a strong belief that the virus spread from E-bola affected people to those animals when they made contact to gain dopaminergic excitation by cushy-mushy feelings and selfies. Precautions to avoid E-bola might include poor LAN facilities (which we already have BTW in our institute), increased research-promotion which the director is promoting at so many levels, and isolation of the diseased which is not possible in a double-seated hostel arrangement. Basically we are prone to E-bola even though reports of Ebola have faintly reached the country. Ebola is eerie in the sense that more than 50% of those affected fail to survive! This does make Ebola more dangerous than E-bola. And it is this argument that they use to spread epidemial quantities of troll memes on the e-world. Stay safe. And remember it is trending on even Google News since a month.

Pharmaceutics to polymers which is identical to oil in water emulsion for parenteral nutrition, but the liquid lipid of the emulsion has been replaced by a solid lipid. They have many advantages such as good biocompatibility, low toxicity, and lipophilic drugs are better delivered by as the solid lipid nanoparticle (SLN), and the system is physically stable. SLN may be a promising sustained release and a drug targeting system for lipophilic drugs. [1] SLNs are composed of physiological and compatible lipids with a high melting point as the solid core, which is coated by nontoxic amphiphilic surfactants as the outer shell. The

Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug.In vitrodrug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and D...

The aim of the current investigation is to evaluate the transdermal potential of novel vesicular carrier, ethosomes, having diclofenac potassium, a potent, water soluble non-steroidal anti-inflammatory drug with lesser transdermal permeation. Drug loaded ethosomes had been prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, invitro skin permeation, skin retention, drug-membrane component interaction and stability. The ethosomal formulation having 4%w/v of phospholipid and 40%v/v of ethanol (F16) showing the greatest entrapment efficiency (72.91±0.64%) with small particle size (251±23nm) was selected for further skin permeation studies. The skin permeation and skin retention studies were performed on ethosomal formulation, liposomal formulation (4%w/v of phospholipid without alcohol), hydroethanolic drug solution and phosphate buffer saline (pH7.4) drug solution. Among them, ethosomal formulation showed higher cumulative percentage of drug permeation (60.37±5%) and more skin retention (619.60±18µg/cm 2 ) after 12 hours than the other formulations. Scanning electron microscopy confirmed the three dimensional nature of ethosomes. Dynamic light scattering technique proved that the ethosomes has smaller vesicular size than the liposomes prepared without alcohol. FT-IR studies revealed no interaction between the drug and membrane components. The ethosomal vesicles were incorporated in carbopol gel base and its anti-inflammatory efficiency was compared with the marketed diclofenac gel. The pharmacodynamic studies showed the enhanced anti-inflammatory activity of ethosomal gel than the marketed gel formulation. Our results suggest that the ethosomes are an efficient carrier for dermal and transdermal delivery of diclofenac potassium.

The aim of the current investigation is to evaluate the transdermal potential of novel vesicular carrier, ethosomes, having diclofenac potassium, a potent, water soluble non-steroidal anti-inflammatory drug with lesser transdermal permeation. Drug loaded ethosomes had been prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, invitro skin permeation, skin retention, drug-membrane component interaction and stability. The ethosomal formulation having 4%w/v of phospholipid and 40%v/v of ethanol (F16) showing the greatest entrapment efficiency (72.91±0.64%) with small particle size (251±23nm) was selected for further skin permeation studies. The skin permeation and skin retention studies were performed on ethosomal formulation, liposomal formulation (4%w/v of phospholipid without alcohol), hydroethanolic drug solution and phosphate buffer saline (pH7.4) drug solution. Among them, ethosomal formulation showed higher cumulative percentage of drug permeation (60.37±5%) and more skin retention (619.60±18µg/cm 2 ) after 12 hours than the other formulations. Scanning electron microscopy confirmed the three dimensional nature of ethosomes. Dynamic light scattering technique proved that the ethosomes has smaller vesicular size than the liposomes prepared without alcohol. FT-IR studies revealed no interaction between the drug and membrane components. The ethosomal vesicles were incorporated in carbopol gel base and its anti-inflammatory efficiency was compared with the marketed diclofenac gel. The pharmacodynamic studies showed the enhanced anti-inflammatory activity of ethosomal gel than the marketed gel formulation. Our results suggest that the ethosomes are an efficient carrier for dermal and transdermal delivery of diclofenac potassium.

The present research work is focused on the development of solid lipid nanoparticles 2 of cefuroxime axetil (CA-SLN) for its enhanced inhibitory activity against Staphylococcus 3 aureus produced biofilm. CA-SLN was prepared by solvent emulsification/evaporation 4 method using single lipid (stearic acid (SA)) and binary lipids (SA and tristearin (TS)). 5 Process variables such as volume of dispersion medium, concentration of surfactant, 6 homogenization speed and time were optimized. The prepared SLN were characterized for 7 encapsulation efficiency, DSC, FT-IR, SEM, AFM, in vitro drug release, stability studies and 8 in vitro anti biofilm activity against Staphylococcus aureus biofilm. Among the process 9 variables, increased volume of dispersion medium, homogenization speed and time led to 10 increase in particle size whereas increase in surfactant concentration decreased the particle 11 size. SLN prepared using binary lipids exhibited higher entrapment efficiency than the single 12 lipid. DSC and FT-IR studies showed no incompatible interaction between drug and 13 excipients. CA-SLN showed two folds higher anti-biofilm activity invitro than pristine CA 14 against Staphylococcus aureus biofilm.

The purpose of this study was to develop a sustained release floating drug delivery system (hollow microsphere or microballoons) of Verapamil hydrochloride using Ethyl cellulose and Eudragit RL 100. Microballoons were prepared by non – aqueous solvent evaporation method and optimized by changing drug: polymer ratio, and polymer combination. Thirteen batches containing only Ethyl Cellulose, only Eudragit RL 100 and both Ethyl Cellulose and Eudragit RL 100 were prepared and evaluated. Drug to Polymer ratio of 1:2 was found to be optimized. Microballoons were stable, white colored, spherical, free flowing in nature and showed controlled release up to 12 hours. The drug release from the microballoons followed Higuchi model indicating diffusion controlled non-Fickian drug release. Optimized formulation batch showed percentage yield 80.99%, percentage buoyancy 84.05±0.93%, particle size 301.17±3.43µm and percentage drug entrapment efficiency 81.45 ± 0.21%.

Background The current research aims to determine the pharmacokinetic parameters, mucoadhesive strength, and IVIVC correlation of the novel chronotherapeutic drug delivery system of montelukast sodium (MTS) loaded Parteck® SRP80 and hypromellose system. To accomplish this, an HPLC method was developed which is highly sensitive, precise, and rapid for quantifying pure MTS in rabbit plasma. Mucoadhesive strength and time-dependent mobility of developed formulation were established by ex-vivo study and X-ray radiography, respectively. Using a fraction of drug absorbed (FDA) and a fraction of drug released (FDR), Level-A in-vitro in-vivo correlation (IVIVC) was developed. According to ICH Q1A (R2) standards, stability experiments were conducted for 180 days. Result MTS retention time came as 3.971 min with a mobile phase of methanol: acetonitrile: 0.2 mM sodium acetate buffer (5:90:5). In-vitro dissolution showed pulsatile release of the drug up to 24 h with two lag phases. The in-vivo ...

Linum usitatissimum Linn. is a widely acclaimed medicinal plant used in every household. The seeds of L. usitatissimum have both medicinal and nutraceutical properties.The study was conducted to evaluate the anti-hypertensive effect of aqueous extract with Secoisolariciresinol Diglucoside (SDG) enriched fraction (SEF) of defatted flaxseeds on fructose-induced hypertension in rats.Hypertension was induced by administration of 10% w/v solution of fructose orally in drinking water. Hypertension developed was confirmed by Systolic blood pressure (SBP) measured after 2 weeks of administration.SEF was given orally once daily at the doses of 50,100 and 200mg/kg. Captopril was given as standard at the dose regimen of 0.05mg/kg once daily for consecutive two weeks. SBP and diastolic blood pressure were measured weekly along with plasma level of glucose, cholesterol, and triglyceride after dissection. Fructose feeding for 4 weeks induced hypertension, increased triglyceride level and increase...

The present study was performed to investigate potential of Eudragit RLPO-based nanosuspension of glimepiride (Biopharmaceutical Classification System class II drug), for the improvement of its solubility and overall therapeutic efficacy, suitable for peroral administration. Nanoprecipitation method being simple and less sophisticated was optimized for the preparation of nanosuspension. Physicochemical characteristics of nanosuspension in terms of size, zeta potential, polydispersity index, entrapment efficiency (% EE) and in vitro drug release were found within their acceptable ranges. The size of the nanoparticles was most strongly affected by agitation time while % EE was more influenced by the drug/polymer ratio. Differential scanning calorimetry and X-ray diffraction studies provided evidence that enhancement in solubility of drug resulted due to change in crystallinity of drug within the formulation. Stability study revealed that nanosuspension was more stable at refrigerated condition with no significant changes in particle size distribution, % EE, and release characteristics for 3 months. In vivo studies were performed on nicotinamide-streptozotocin-induced diabetic rat models for pharmacokinetic and antihyperglycaemic activity. Nanosuspension increased maximum plasma concentration, area under the curve, and mean residence time values significantly as compared to aqueous suspension. Oral glucose tolerance test and antihyperglycaemic studies demonstrated plasma glucose levels were efficiently controlled in case of nanosuspension than glimepiride suspension. Briefly, sustained and prolonged activity of nanosuspensions could reduce dose frequency, decrease drug side effects, and improve patient compliance. Therefore, glimepiride nanosuspensions can be expected to gain considerable attention in the treatment of type 2 diabetes mellitus due to its improved therapeutic activity.

Increased prevalence of oral diseases such as gingivitis, periodontitis and dental caries has become major health issue worldwide. Such growing incidence of periodontitis has directly affected the development of drug delivery systems and growth of the market. Since the infections are limited to periodontal pockets or oral cavity, localized intrapocket drug delivery will be more beneficial than conventional systemic administration. Advances in intrapocket technology and innovations in the field of periodontal drug delivery led to increased patent applications. Newer trends like use of mucoadhesive polymers, in situ forming gels, viscosity modifiers, plasticizers etc which can enhance intrapocket retention of drugs have gained considerable attention among researchers and industrialists. Current market is flooded with products such as Periostat, Periochip ® , Atridox ® , Arestin ® , Actisite ® , Dentomycin ® , and Elyzol ® and generics such as metronidazole, levofloxacin, tetracycline, doxycyline and minocycline for intrapocket delivery. There is a need of novel drugs and delivery systems with better efficacy profiles than the existing compounds. Inclusion of novel technologies like films, fibers, in situ forming implants, microparticles, nanoparticles, and liposomes as intrapocket drug delivery has great potential. Development of antibiotic free drug delivery such as antiseptics, host modulators, biofilms inhibitors and antibodies has promising role in the improvement of pathogenesis of periodontitis. Further, this review deals with various innovations in drug delivery and patents related to localized intrapocket administration of medicaments in the implications of periodontitis.

Periodontal disease is chronic, highly prevalent infectious disease that requires prolonged and controlled delivery of antimicrobial agents into pockets. To achieve this objective, dual antimicrobials encapsulated chitosan fortified calcium alginate (CS-Ca-SA) microspheres were formulated by application of Plackett-Burman factorial design. The microspheres were optimized for particle size (PS), entrapment efficiency (EE) and drug release. The optimized microspheres presented average PS of 74-461 µm and EE of 62.45-86.20% with controlled drug delivery for 120 hours. FTIR disclosed successful complexation between SA and CS. DSC and XRD studies showed changes in the crystallinity of drugs in microspheres. Shape factor and SEM demonstrated spherical to pear-shaped microspheres. Release exponent &gt;0.43 and high diffusion coefficients revealed non-Fickian-based diffusion-limited drug release. CS-Ca-SA microspheres exhibited surface pH of 6.5 ± 0.5, moderate swelling, less erosion and im...