Rubia cordifolia L. Attenuates Diabetic Neuropathy by Inhibiting Apoptosis and Oxidative Stress in Rats.

BACKGROUND: Diabetic neuropathy is a debilitating manifestation of long-term diabetes mellitus. The present study explored the effects of the roots of Rubia cordifolia L. (R. cordifolia L.) in the Wistar rat model for diabetic neuropathy and possible neuroprotective, antidiabetic, and analgesic mechanisms underlying this effect. MATERIALS AND METHODS: Rats were divided into five experimental groups. An amount of 0.25% carboxy methyl cellulose (CMC) in saline and streptozotocin (STZ) (60 mg/kg) was given to group 1 and group 2, respectively. Group 3 was treated with STZ and glibenclamide simultaneously while groups 4 and 5 were simultaneously treated with STZ and hydroalcoholic extract of the root of R. cordifolia, respectively. Hot plate and cold allodynias were used to evaluate the pain threshold. The antioxidant effects of R. cordifolia were assessed by measuring Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). At the end of the study, sciatic nerve and brain tissues were collected for histopathological study. Bcl-2 proteins, cleaved caspase-3, and Bax were assessed through the Western blot method. RESULTS: R. cordifolia significantly attenuated paw withdrawal and tail flick latency in diabetic neuropathic rats. R. cordifolia significantly (p < 0.01) improved the levels of oxidative stress. It was found to decrease blood glucose levels and to increase animal weight in R. cordifolia-treated groups. Treatment with R. cordifolia suppressed the cleaved caspase-3 and reduced the Bax:Bcl2 ratio in sciatic nerve and brain tissue compared to the diabetic group. Histopathological analysis also revealed a marked improvement in architecture and loss of axons in brain and sciatic nerve tissues at a higher dose of R. cordifolia (400 mg/kg). CONCLUSION: R. cordifolia attenuated diabetic neuropathy through its antidiabetic and analgesic properties by ameliorating apoptosis and oxidative stress.

Development and evaluation of Hedyotis corymbosa (L.) extract containing phytosomes: a preclinical approach for treatment of neuropathic pain in rodent model.

PURPOSE: The study was aimed to encapsulate Hedyotis corymbosa extract (HCE) into phytosomes to improve its therapeutic efficacy in neuropathic pain by enhancing the bioavailability of chief chemical constituent Hedycoryside -A (HCA). METHODS: For preparing phytosomes complexes (F1, F2, and F3), HCE and phospholipids were reacted in disparate ratio. F2 was chosen to assess its therapeutic efficacy in neuropathic pain induced by partial sciatic nerve ligation. Nociceptive threshold and oral bioavailability were also estimated for F2. RESULTS: Particle size, zeta potential and entrapment efficiency for F2 were analysed as 298.1 ± 1.1 nm, -3.92 ± 0.41 mV and 72.12 ± 0.72% respectively. F2 gave enhanced relative bioavailability (158.92%) of HCA along with a greater neuroprotective potential showing a significant antioxidant effect and augmentation (p < 0.05) in nociceptive threshold with the diminution in damage to nerves. CONCLUSION: F2 is an optimistic formulation for enhancing the HCE delivery for the effective treatment of neuropathic pain.

Potential Assessment of Topical Felbinac-Loaded Cubosomal Gel in Soft Tissue Injury in Albino Rats.

Muscle strain is one of the most common injuries with high intermittence rate. Due to diverseness of strain injuries, different experimental animal models are employed to investigate such injuries with reproducible results. Cubosomes, an emerging nano drug delivery tool, are considered ideal carriers for the topical delivery of lipophilic drugs to treat local inflammations with reduced frequency of application for prolonged periods. This work describes the development of Felbinac-loaded cubosomal gel and investigated the treatment of inflammation and tissue injury in vivo. Sciatic Function Index (SFI) is a simple clinical method to observe hind limb recovery in rats after induced injuries. First, cubosomes were fabricated by high-pressure homogenization process and evaluated for in vitro parameters. The optimized cubosome formulation was chosen to develop cubosomal gel and evaluated for in vitro parameters and also investigated time to recovery of SFI after strain induction in tibialis anterior muscles in rats. The cubosome formulation (F4) exhibited low droplet size (51.04 ± 1.37 nm)and polydispersity index (0.085 ± 1.13), and negative zeta potential (-32.8 ± 0.67 mV). In rats, topical application of cubosomal gel formulation (CGF) exhibited significant improvement in skin permeation (402 ± 6.08 µg) and drug flux (15.71 ± 0.82 µg/cm2 h) compared to plain gel. Also, CGF demonstrated significant difference in SFI from first to seventh day. The histology of rat skin showed significant effect for groups treated with Felbinac-loaded CGF compared to a negative control group.

Development of Topical Nanoemulgel Using Combined Therapy for Treating Psoriasis.

This study focuses on the development of topical formulation of methoxsalen using Babchi oil as formulation component that can be applied at body surfaces providing sustained delivery and enhanced penetration of methoxsalen leading to significant epidermal localization and better anti-psoriatic activity. The combination of psoralens, that is, methoxsalen (synthetic) and Babchi oil (natural) has been developed into nanoemulgel formulations. A total of four nanoemulsion formulations was developed using Babchi oil as oil phase and Tween 80 as surfactant by high-pressure homogenization method. The prepared nanoemulsions were characterized for entrapment efficiency, mean droplet size, and zeta potential. Based on characterization results, the optimized nanoemulsion formulation(s) were incorporated into the carbopol gel base to make a nanoemulgel. The prepared nanoemulgel formulations were analyzed for pH, drug content determination, spreadability, viscosity, ex vivo skin permeation, and in vivo studies. The nanoemulsions showed droplet size between 51.3 and 146.7 nm, entrapment efficiency of 92.76%-98.10%, and zeta potential of -28.1 to -54.89 mev. The nanoemulsions showed varied in vitro drug release. In ex vivo skin permeation, nanoemulgel (NG2) showed increased penetration and localized accumulation of methoxsalen across the skin compared with plain gel. Ex vivo results were substantiated by in vivo results showing significant amelioration of hyperproliferative skin symptoms. The promising results suggested that nanoemulgel system is a suitable carrier for the topical delivery of methoxsalen-Babchi oil.

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, w/w) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.

Fabrication of Mupirocin-Loaded Nanostructured Lipid Carrier and Its In Vitro Characterization.

In the present study, mupirocin (MP), an antimicrobial agent, was formulated as a nanostructured lipid carrier (NLC) by using a novel method named as melt emulsion ultrafiltration method. For the formulation of NLC, glyceryl monostearate and watermelon seed oil were used as solid and liquid lipids, respectively. The method was optimized for various parameters by Taguchi design of experiment and prepared NLCs were characterized for particle size, polydispersity index (PDI), shape, zeta potential, % drug loading, and in vitro release profile. The optimized NLCs were found to be smooth, monodisperse with PDI 0.229 ± 0.093. NLCs were found to have an average particle size of 139 ± 0.75 nm and +21.9 ± 0.98 mV as zeta potential. The % drug loading of optimized NLCs was found to be 59% ± 0.13%. The optimized NLCs were able to release the drug up to 24 h. The release kinetic study revealed mixed-order kinetics. Hence, it was concluded that the novel method is simple and able to fabricate MP-loaded NLCs with sustained release property and being stable in terms of particle size, PDI, and % drug loading.

Formulation Development of Topical Preparation Containing Nanoparticles of Povidone-Iodine for Wound Healing.

Povidone-iodine (PVI) is an antiseptic drug that is used for wound healing or for repair of the damaged tissue. Studies on solid lipid nanoparticles (SLNs) indicate that this system could potentially be used as a delivery system with improved drug entrapment efficiency and controlled drug release for hydrophilic actives. This study focuses on developing a topical gel containing SLNs of PVI for wound healing. SLNs were prepared by using the solvent emulsification diffusion method. Lipids such as glycerol monostearate, palmitic acid, and stearic acid, and surfactants such as polysorbate 80, soyalecithin, and Pluronic F-68 were used for the preparation of SLN. These were screened out based on particle size and entrapment efficiency of SLN. Gel was prepared by using Carbopol 940 (1% w/w) and propylene glycol (10% w/w). Formulated SLNs were evaluated by various in vitro and in vivo techniques. Based on the results, the drug-to-lipid ratio (1:3) and 2% polysorbate 80 (surfactant) along with stirring rate (3,000 rpm) produced the desired particle size (285.4 nm) with good stability. 22.85% drug loading and 88.83% drug entrapment efficiency were found in the optimized formulation. In vitro drug release shows that it follows the Korsmeyer-Peppas model. The animal study shows that the period of epithelization produced by the test group was 17.14 ± 1.35 days, which was near to that of the standard group (16.25 ± 1.24 days). Clinical Trial Registration number: 1044/PO/Re/S/07/CPCSEA.

Formulation of Herbal Fast Disintegrating Tablets and its ex-vivo Study for Anti-histaminic Activity in Guinea Pig Ileum.

OBJECTIVE: The aim of present research work was to develop a herbal fast disintegrating tablet containing Fagonia schweinfurthii Hadidi dried extract and determining its antihistaminic activity using guinea pig ileum. METHOD: The tablets were formulated by wet granulation technique using three different superdisintegrants (croscarmillose, crospovidone and sodium starch glycolate) at three different levels. The tablets were evaluated for various physical properties like hardness, friability weight variation etc. and various mechanical properties like disintegration time, wetting time to select the best superdisintegrant. The selected superdisintegrant was further used as intra as well as extra granulating agent to develop fast disintegrating tablets of Fagonia schweinfurthii Hadidi dried extract. The optimized formulation was subjected to stability study as per the ICH guidelines. Finally, Ex-vivo antihistaminic study was conducted on guinea pig ileum for optimized formulation and compared with marketed tablet containing cetrizine HCl as API (Stanhist-10, Ranbaxy, Pvt. Ltd). RESULTS: Physical properties of all tablet batches were found to be acceptable and comply with various official specifications. The disintegration time and wetting time of optimized formulation (F'3) were found to be 1.15±0.08 and 0.56±0.04 min respectively. Results of Ex-vivo study showed a comparable histamine inhibition between optimized tablet (15%) and marketed tablet formulation (18.8%) in a dose of 5 µg/ml. CONCLUSION: On the basis of in-vitro and Ex-vivo studies, it was concluded that prepared herbal fast disintegrating tablets were stable and had potent antihistaminic activity.

An Overview on Bacteriophages: A Natural Nanostructured Antibacterial Agent.

BACKGROUND: Recent advances in the field of bionanomedicine not only enable us to produce biomaterials but also to manipulate them at molecular level. Viruses particularly bacteriophages are a promising nanomaterial that can be functionalized with great precision. Bacteriophages are the natural antimicrobial agents that fight against antibiotic resistant bacteria which cause infections in animals, humans, or in crops of agricultural value. The idea of utilizing bacteriophages as therapeutic agents is due to their ability to kill bacteria at the end of the infectious cycle. OBJECTIVE: This paper reviewed the general biology of bacteriophages and the presence of receptors on the bacteria which are necessary for the recognition and adsorption of bacteriophages. Pharmacokinetics and therapeutic potential of bacteriophages administered through various routes in treating diverse bacterial infections is also reviewed along with the problems associated with bacteriophage therapy. CONCLUSION: Among various routes of administration, parenteral route is found to be the most thriving route for the treatment of systemic infections whereas oral route is meant to treat gastrointestinal infections and; local delivery (skin, nasal, ears) of phages has proven its potency to treat topical infections.

Solid Lipid Nanoparticles Approach for Lymphatic Targeting Through Intraduodenal Delivery of Quetiapine Fumarate.

BACKGROUND: Lymphatic route is one of the prominent routes for improving the poor bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the bioavailability enhancement along with controlled and site specific drug delivery. OBJECTIVE: The aim of the present research work was to prepare and optimized the Quetiapine fumarate (an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal administration. METHOD: Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed using different lipids by Microemulsion technique and optimized by box behnken design. RESULTS: Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference (P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation. In vitro release data of optimized formulation (Q9) was subjected to zero order, first order and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal administration and several pharmacokinetic parameters were determined. AUC (0-∞) of optimized formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with that of drug suspension. CONCLUSION: On the basis of results of in vitro study, Q9 formulation was selected as optimized formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic delivery.

New Drugs and Vaccines for Tuberculosis.

BACKGROUND: Tuberculosis (TB) is an infectious disease that resulted in estimated 9.6 million new cases in 2014 and 1.5 million deaths. The available drug regimen for TB is time consuming which more often leads to the patient non compliance which then results in occurrence of drug resistant TB (Multi-drug and extremely drug resistant TB) in several portions of the world. METHODS: The dangerous combinations of TB and HIV is taking its toll on human health. The foremost factor is non- profit associated with the development of anti TB drugs. There is almost 10 different drugs in various levels of trials whereas the vaccine development is focusing more on adult vaccine rather than a child vaccine. RESULTS: More than 15 vaccine candidate are in various stages of pipelines. Present compilation gives an account for various drug candidates and vaccine products in various stages of drug development. Also included is a recent collection of patents for assay methods, potential drug candidates/classes and vaccination products. CONCLUSION: The need is for improvement in the activity and chemical and biological description of under development compounds. Lastly the set up for clinical and appropriate uses for running a reliable clinical trial is a necessary prerequisite.

Chitosan based in situ forming polyelectrolyte complexes: A potential sustained drug delivery polymeric carrier for high dose drugs.

The present study investigated the feasibility of using combination of Cationic and anionic polymers as sustained release carrier for the delivery of high dose gastric acid soluble model drug Paracetamol. Various formulations were prepared using wet granulation technique. Briefly a cooled (4°C) neutral solution of chitosan (CH) was combined with cooled aqueous solution (4°C) of anionic polymer such as Gum Ghatti (GG) and Xanthan gum (XG). This polyelectrolyte solution was then used to granulate the model drug Paracetamol. The prepared tablets were evaluated for various pharmacopoeial and non pharmacopoeial parameters viz. Thickness, Hardness, Friability, Weight Variation, Content uniformity and Drug Content. The drug release study carried out in 0.1M HCl revealed in situ Polyelectrolyte complex formation (PEC) between CH and anionic biopolymers. This in situ PEC formation resulted in sustained delivery of high dose gastric fluid soluble drug Paracetamol. Further, effect of incorporation starch and lactose as tablet diluents on release rate was also studied. It was observed that paracetamol release from lactose granulation was faster than tablets prepared with starch as diluents. From the data generated it was concluded that In situ PEC formation approach has sufficient potential to sustain the release of drugs like paracetamol.

Nanovesicles of nitrendipine with lipid complex for transdermal delivery: pharmacokinetic and pharmacodynamic studies.

CONTEXT: Vesicular transdermal delivery can enhance the bioavailability of a drug especially affected by first-pass metabolism, e.g. nitrendipine. However effective transdermal delivery employs permeation enhancer, e.g oleic acid (OA) with ceramide 2, stearic acid, behenic acid, and cholesteryl sulfate lipid complex. OBJECTIVE: This study investigated the preparation, characterization of physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential in rats, of nitrendipine-loaded nanovesicles of ceramide 2, stearic acid, behenic acid and cholesteryl sulfate containing oleic acid gel (NOVG). MATERIALS AND METHODS: The nanovesicles were made using film hydration method and characterized for physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential. RESULTS: Nitrendipine-loaded nanovesicles of ceramide-2 containing oleic acid (NOV-5) have shown fluxes in the range of 4.88-24.72 µg/cm(2)/h nitrendipine oral suspension (NOS) at equal dose. NOVG-5 has shown almost 33% reduction in blood pressure in the first hour and a further decrease of 25% in the second hour to restore the normal pressure. DISCUSSION: The permeation increases with increase in OA content. OA gets integrated in vesicle wall and enhances its permeability, whereas ceramide content makes sure that skin does not become damaged even after permeation. CONCLUSION: NOVG-5 has shown the most favorable physicochemical properties and good permeation through skin providing good management of hypertension during crucial initial hours.

Development of ibuprofen nanoliposome for transdermal delivery: Physical characterization, in vitro/in vivo studies, and anti-inflammatory activity.

OBJECTIVE: Ibuprofen is an established non-steroidal anti-inflammatory drug commonly used for general inflammation. However, it causes gastrointestinal troubles when administered orally, thereby decreasing patient compliance. Transdermal application of vesicular formulation of Ibuprofen will provide better patient compliance and efficacy. METHODS: Six different compositions of lipid constituents have been formulated into nanovesicles using thin-film hydration method and dispersed into gel using Carbopol 934. The formulations were characterized based on physicochemical parameters using photon correlation spectroscopy, transmission electron microscopy, in vitro drug release, ex vivo skin permeation using human skin, and in vivo studies. RESULTS: The formulation, ibuprofen liposomal gel-5 (ILG-5), had nanoliposome of smallest size (159 nm) and polydispersity index (0.331). This formulation showed moderate zeta potential and the highest encapsulation. All the formulations including IG showed a considerable amount of drug release through in vitro synthetic membrane. ILG-5 showed maximum permeation during skin permeation studies. IG showed no permeation in ex vivo settings. ILG-5 has shown the highest Cmax and AUC during in vivo permeation study. CONCLUSIONS: The present work clearly shows the superiority of nanoliposome formulation over non-vesicular formulations and that lipid composition containing 7/3/1 molar ratio of phosphatidylcholine, cholesterol, and dicetyl phosphate is optimum for nanoliposome preparations, in the cases where controlled delivery of drug is needed for a sufficient period of time.

Enhanced oral bioavailability of efavirenz by solid lipid nanoparticles: in vitro drug release and pharmacokinetics studies.

Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6-98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (C max) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES).

Phytochemical, therapeutic, and ethnopharmacological overview for a traditionally important herb: Boerhavia diffusa Linn.

UNLABELLED: Boerhavia diffusa (BD) is a plant of rasayana category as per ayurvedic claims. It is reported to possess antiaging, disease prevention, and life strengthening activities which hold enormous influence in disease burden and affordability/availability of healthcare in the world. Objective. This paper has been compiled to comment on the studies reported for BD to highlight its chemical and therapeutic potential along with its ethnopharmacological considerations. METHODS: In the present paper, a detailed account of chemical constituents and pharmacological activities has been presented. All the findings were correlated with modern pharmacological activities to appraise the value of BD. RESULTS: Chemical analysis of BD gives a wide variety of chemical constituents, namely, rotenoids, flavonoids, xanthones, purine nucleoside, lignans, and steroids. Various ethnopharmacological reports emphasize its role in disorders of reproductive system, gastrointestinal system, respiratory system, urinary system, hepatic system/jaundice, cardiovascular system, and cancer. CONCLUSIONS: The studies on the therapeutic activities of BD range from studies on crude extracts to isolated compounds; however some of the studies require sophistication and validated results. BD is a plant of enormous importance in the purview of its chemical and therapeutic properties.

Formulation and evaluation of guggul lipid nanovesicles for transdermal delivery of aceclofenac.

CONTEXT: Most new drugs have low water solubility and liposome is an important formulation to administer such drugs; however, it is quite unstable and has negligible systemic absorption. OBJECTIVE: Aceclofenac nanovesicles were made using guggul lipid for formulating stable transdermal formulation. MATERIALS AND METHODS: Guggul lipid was formulated into vesicles along with cholesterol and dicetyl phosphate using film hydration method. The formulations were analyzed for physicochemical properties and stability. Then its skin permeation and anti-inflammatory activity were determined. RESULTS: Both categories of vesicles (PC and GL) showed optimum physicochemical properties; however, accelerated stability study showed considerable differences. GL-1 was appreciably stable for over 6 months at 4 °C. Corresponding gels (PCG-1 and GLG-1) showed C max values at 4.98 and 7.32 µg/mL along with the Tmax values at 4 and 8 hours, respectively. GLG-1 inhibited edema production by 90.81% in 6 hours. Discussion. PC liposomes are unstable at higher temperature and upon longer storage. The formulation with higher lipid content (GL-1) showed good drug retention after 24 hours and appreciable stability both at higher temperature and for longer duration. Guggul lipid being a planar molecule might be stacked in vesicle wall with cholesterol. CONCLUSION: The composition of the nanovesicle played an important role in stability and drug permeation. Guggul lipid is suitable for producing stable vesicles.

Ceramide-2 nanovesicles for effective transdermal delivery: development, characterization and pharmacokinetic evaluation.

UNLABELLED: Abstract Context: The vesicles based on skin lipid have a drug localization effect and its main lipid, ceramide provides protective and regenerative effects while oleic acid (OA) is a penetration enhancer, however, it causes slight irritation, so we have formulated formulation incorporating both of these to develop a transdermal formulation for better permeation. OBJECTIVE: Present study investigated the preparation and characterization of physicochemical properties and permeation of nanovesicles of ceramide-2 containing OA and palmitic acid (PA) respectively and a commercial gel. MATERIALS AND METHODS: The vesicles were made using ceramide 2, cholesterol (Chol), cholesteryl sulfate (CS) and OA or PA, respectively, using film hydration method. The vesicles were characterized for physicochemical properties, ex vivo permeation using human skin and pharmacokinetic parameters and anti-inflammatory activity in rats. RESULTS: The vesicles showed size at 102-125 nm while PDI was 0.11-0.13 and negative zeta potential. OV-3 showed highest entrapment efficiency. The drug fluxes were 92.02 and 8.920 µg/cm(2)/h, respectively, for OV-3 and PV-1. The Cmax were 7.91 and 4.01 µg/ml at 4 and 6 h for OV-3 (2.5 mg) and PV-1 (10 mg), respectively. OV-3 and PV-1 showed 98.8% and 77.36% edema inhibition, respectively, at 3 h. DISCUSSION: Both formulations showed similar physical parameters and different permeation since OA get incorporated in vesicles and increases its permeability and ceramide makes sure that vesicles can rapidly traverse the stratum corneum. CONCLUSION: OV-3 containing 3% OA showed optimum physical parameters and good permeation with maximum anti-inflammatory activity.

Development of a new nanovesicle formulation as transdermal carrier: formulation, physicochemical characterization, permeation studies and anti-inflammatory activity.

CONTEXT: Ibuprofen is an important NSAID, however, it can cause GI disturbances when given orally, and employment of transdermal route will require permeation enhancer causing skin injury. OBJECTIVE: Drug-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, and cholesteryl sulfate (ICVG) were formulated and analyzed for physicochemical and permeation properties. MATERIALS AND METHOD: Vesicles were formulated using film hydration method and physicochemical parameters, in vitro drug release, and stability were assessed. Further, nanovesicle gels were evaluated against plain gel containing drug (CG) for ex vivo/in vivo drug permeation and anti-inflammatory activity. RESULTS: The developed formulations showed optimal physicochemical profile and ICV-1 gave 97.24% drug release. Drug permeation was between 17.32 and 33.12 µg/cm(2) for ICVG formulations and 0.27 µg/cm(2) for CG. ICVG-1 and CG showed Cmax of 9.6 and 0.7 µg/ml at 8 and 4 h. ICVG-1 showed 19.9 times higher AUC than CG. Edema inhibition was 57.98% during initial hours by ICVG-1. DISCUSSION: Ratio of ceramide 2 and palmitic acid plays a critical role in drug permeation through stratum corneum. The stability and protective effect of the formulations were due to ceramide content. CONCLUSION: The composition has an important role in physicochemical properties and drug permeation thereby generating an optimum formulation.

Development and optimization of gastroretentive mucoadhesive microspheres of gabapentin by Box-Behnken design.

CONTEXT: Gabapentin follows saturation kinetics for absorption because of carrier-mediated transport and narrow absorption window in stomach. There is need to develop a gastroretentive formulation to maximize the absorption without crossing the saturation threshold for absorption. OBJECTIVE: The aim was to develop a gastroretentive formulation of gabapentin to increase the fraction of drug absorbed in stomach. MATERIALS AND METHODS: Sodium alginate and sodium carboxymethylcellulose were used to formulate the microsphere by ionotropic gelation with calcium chloride. The formulation was optimized using a three-factor, three-level Box-Behnken design. RESULTS: The particle size varied from 559.50 to 801.10 µm, entrapment efficiency from 61.29 to 81.00% and in vitro release from 69.40 to 83.70%. The optimized formulation was found using point-prediction, and formulation OF-3 showed optimum results at 608.21 µm size, 79.65% entrapment efficiency and 82.72% drug release and 81% mucoadhesion up to 10 h. The drug release was controlled for more than 12 h. DISCUSSION: The particle size was most influenced by sodium alginate while entrapment efficiency and drug release depended upon both polymers. The release followed Higuchi model. CONCLUSION: Gastroretentive formulation was successfully optimized by a three-factor, three-level Box-Behnken design and found to be useful.