Iranian Journal of Pharmaceutical Sciences

The available minoxidil formulations for topical application suffer with major drawback having less contact time with the scalp which requires repeated application. Hence, the present study was aimed to investigate the effect of microemulsions and microemulsion based hydrogel systems (MEHs) for increased percutaneous penetration of minoxidil. Minoxidil microemulsions were developed by following conventional titration method using oleic acid as oil phase, Tween 80 as surfactant and polyethyleneglycol 200 as co-surfactant. Smix is a surfactant and co-surfactant mixture, whose ratios in the mixture were optimized using the pseudo ternary phase diagram. The physicochemical interaction between the drug and polymer were investigated by FTIR. Prepared microemulsions and MEHs were evaluated for drug content, viscosity, pH, in vitro, ex vivo permeation, skin irritation and stability studies. The drug content and viscosity in prepared microemulsions was found ranged from 56.77±2.88 to 92.85±1.59 %, and 89.12±1.801 to 144.24±0.95 cps respectively. The Ex vitro skin permeation from these microemulsions was sustained over 24 h with drug release around 32±3.26 to 99±3.78 % with more retardation in formulation F4 (oleic acid:Smix:water 58%:40%:2%). F4 was incorporated into hydroxypropyl cellulose gel to get MEH formulation and both were compared with the marketed topical solution. Marketed preparation was diffused at faster rate in comparison to the microemulsion and MEH. The drug release order was found to be Higuchi’s with non-Fickian “anomalous” mechanism at controlled rate. The flux of the microemulsion F4 and MEH was found around 70.11±10.81 and 90.26±11.46 (μg/cm2/hr) with permeation coefficient around 27.18±6.69 and 30.21±5.16 (cm/hr). The microemulsion did not show any dermatological reactions when tested. The microemulsion was found stable on storage and results suggested that microemulsions and MEHs could be more promising for topical delivery of minoxidil in hair loss treatment in comparison to solution based formulations.

Herbal medicine has an old history with a broad application all over the world. Many researches have focused on the curative as well as antinociceptive effects of herbal extract. The aim of this study was to investigate the analgesic effects of Berberis vulgaris hydroethanolic extract (BVE) in male mice. 30 male mice were divided into 5 groups: control, treated by morphine, treated by BVE (150 & 300 mg/kg) and naloxane plus BVE (300 mg/kg) randomly. To assess the antinociceptive effects of BVE, the animals were examined by employing different pain models such as, tail-flick tests (for acute pain) and acetic acid-induced writhing (for chronic pain) after treatment with morphine, naloxane and BVE. The results indicate that the BVE showed an important antinociceptive effect at doses of 150 and 300 mg/kg (P<0.01 and P<0.001, respectively), administered intraperitoneally in mice, which significantly inhibited the abdominal constrictions (55.73% of inhibition) induced by acetic acid and increase tail-flick latency when compared to control group in the same dose, although they were less effective than morphine in the same assay. The antinociceptive models employed here reveal a potential analgesic effect of the Berberis vulgaris hydroethanolic extract. We suggest that this effect might be caused by anti-inflammatory effect and the stimulation of the opioid receptors.

Till date, most of the drugs have been given in conventional immediate release dosage form. Nimorazole is an anticancer drug, used as a hypoxic radiosensitizer in patients undergoing radiotherapy and no formulation has been available in the market till now. Hence, for the purpose to develop an immediate release dosage form, a statistical optimization process has been employed to quantify the effect of two primary excipient MCC and maize starch on its immediate release characteristics. A series of combinations by varying the composition of the two excipients were prepared and their effect on tablet property such as disintegration time, hardness and friability were analyzed using statistical design software. An optimized formulation generated by the software, was evaluated for tablet properties and drug-excipient compatibility study was carried out by FT-IR analysis and DSC thermogram analysis. A SEM image of the granules was recorded to study surface morphology. A 70:50 combination of MCC and starch was found to be the best optimized formulation for an immediate release tablet without affecting its hardness and stability. Disintegration time increased with increasing amount of starch, but decreased with increasing amount of MCC. The low prediction error observed during evaluation of the final formulation indicated the high prognostic capability of the RSM methodology. FT-IR and DSC study confirmed the compatibility of the drug with excipients.

Preparation and characterization of thermoresponsive in-situ forming poloxamer hydrogel for controlled release of Nile red-loaded solid lipid nanoparticles. Nanoparticles (NPs) are cleared rapidly from systemic circulation and do not provide sustained action in most cases. To solve this problem, this investigation introduces an erodible in-situ forming gel system as potential vehicles for prolonged release of NPs. In this study, Nile red-containing SLNs were prepared by solidification of an oil-in-water microemulsion using stearic acid, surfactants and co-surfactants. SLN particles were then loaded in a Poloxamerthermoresponsive sol-gel matrix. Dialysis membrane and membrane-less diffusion method were used to study release of the fluorescent probe. Erosion test were carried out by gravimetric method and the medium was checked for zeta potential to investigate existence of intact SLNs. Sol-gel transition temperature was determined by stirring method. Release results showed high entrapment of Nile red in lipid matrix of SLN. Therefore, Nile red content in erosion medium was attributed to SLN particles. Zeta potential of SLNs remained unchanged after sol-gel loading (P>0.05). The correlated released amount of Nile red to dissolved gel weight implied erosion could be major mechanism of SLN release. Results also showed that SLN increase erosion rate of Poloxamer gel and its sol-gel transition temperature. The present study show that thermoresponsivePoloxamer gel can be used to control the release of NPs and those intact NPs are released from this system. The prepared formulation can be used for further investigations in vivo.

Substituted 1, 2, 4- Triazoles have shown multiple biological activities such as anti-inflammatory, anti fungal, etc. 5-mercapto triazoles were prepared from the potassium dithiocarbazinates. These triazoles were used for preparation of different derivatives by two different schemes. In the first scheme the Mannich bases were prepared from 5- marcapto-s triazole Quinazolines. The 5-Marcato-s-Triazole Quinazolines were synthesized from 5-Marcapto-s-Trizole by reacting with the Quinazoline benzoic acid or acid chlorides. In the second scheme, the synthesis of Quinazolyl Triazolo Thiadiazole Derivatives were prepared by the reaction of Quinazoline benzoic acid and 5-Marcapto-s –Triazoles in POCl3.All the newly synthesized compound structures were elucidated using various spectral techniques viz. IR, 1HNMR and screened for in vitro antibacterial and anti fungal activities. Anti bacterial activity was carried out against organisms Bacillus pumilus, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli as well as anti fungal activity were carried out against A.Nigier and C.Albicans. The results substantiated that the synthesized compounds were effective against bacteria, fungi.

We aimed to evaluate the potential of growing rats as a model of osteoporosis induced by short term hypercholesterolemia. Twelve growing female Sprague-Dawley rats were randomly allocated into two groups. Control rats received standard diet while rats in group 2 were fed with diet contained 20% sunflower oil, 2% cholesterol and 0.5% cholic acid for 2 weeks and then a diet contained 10% sunflower oil, 1% cholesterol and 0.25% cholic acid for the next 4 weeks. At the end of second week, serum total cholesterol level was assayed which was repeated at the end of the 6th week along with serum carboxy-terminal collagen crosslinks (CTX) and procollagen type 1 N propeptide (PINP) levels. Finally, rats were euthanized and right and left tibiae were dissected for histomorphometric study and determination of bone mineral density, respectively. Hypercholesterolemia was present in rats of group 2 in both sampling times. No significant difference was observed in body weight, epiphyseal and metaphyseal histomorphometric parameters and mineral density as well as serum CTX and PINP. Although this was a preliminary study with relatively low sample size, it seems that growing female Sprague-Dawley rats do not show bone loss due to short term hypercholesterolemia and may not be a proper animal model in this regard.

Growing interest to use natural preservatives and spices with antimicrobial effects and large amounts of floral bio-residues (92.6 g per 100 g) generated and wasted in the production of saffron spice guided this study to evaluate the opportunity to expand the uses of C. sativus flowers (petals and stamens), beyond the spice (dried stigmas). The antibacterial potential of total extracts and different sub-fractions of floral bio-residues of saffron production (petals and stamens) were primarily evaluated against five bacterial strains potentially causing food-borne disease (Bacillus cereus, Staphylococcus aureus, Salmonella enterica, Escherichia coli and Shigella dysenteriae) using well diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined by macrodilution method. Methanol extract of petals had shown more antibacterial activity against S. aureus, S. enteric, and S. dysenteriae compared to stigma. Methanol extract and ethyl acetate sub-fraction of stamens showed more antimicrobial effect against B. cereus and E. coli. The petals total extract showed the most antibacterial activity against Shigella dysenteriae (MIC 15.6mg/ml) while the ethyl acetate and chloroform sub fractions showed the maximum effect against Bacillus cereus(MIC 62.5mg/ml). Stamen methanol total extract and aqueous sub fraction have the maximum effect against Staphylococcus aureus and Bacillus cereus (MIC 62.5mg/ml) while the ethyl acetate sub fraction has the best effect against Shigella dysenteriae (MIC 15.6mg/ml). Results showed that both petals and stamens could act as new and natural sources of antibacterial agents with food industrial applications.

There is the need for new drugs with better action and lesser side effects. A lot of research is being undertaken to find out new plant drugs, their extraction and pharmacological evaluation. One of such plant is Curcuma aromatica whichbelongs to the genus Curcuma and reported to have high ethno-botanical values in traditional medicine. The present study evaluates comparative pharmacological activity of four different extracts of Curcuma aromaticain healthy Wistar strain albino rats.Extraction of active constituents from powdered plant rhizomes was done by cold maceration technique using water, ethanol, hydroalcohol and toluene as solvents separately to get respective extracts. Acute oral toxicity study was performed to determine toxicity or side effects associated with the prepared plant extracts. The extracts were evaluated for anti-diabetic, anti-oxidant, anti-inflammatory and analgesic activity. Anti-diabetic activity was comparatively evaluated in alloxan induced diabetic rat models. Toluene extract was found to have relatively higher anti-diabetic activity. In vitro antioxidant potential of different extracts of was evaluated by DPPH radical scavenging activity. The results show anti-oxidant potency in toluene extract slightly better than other extracts. Aqueous extract of Curcuma aromatica rhizomes was found to have more potency in treatment of carrageenan induced paw oedema and also in its anti-nociceptive action against heat induced pain by Eddy’s hot plate method in rats.Though the anti-diabetic and anti-oxidant activities were slightly superior in toluene extract, the risk of residual amount of toluene remained in the final extract and its teratogenic property subdues its benefits of treatment.Findings of this research prove our hypothesis that oral administration of aqueous rhizome extract has potential anti-diabetic, anti-oxidant, anti-inflammatory and analgesic activities.