DEVELOPMENT OF FROVATRIPTAN SUCCINATE MICROEMULSION FOR NASAL DELIVERY: OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

Objective: The main objective of the present research work was to develop, optimize, and characterize microemulsion (ME) of frovatriptan succinate to improve brain transport. Methods: The pseudoternary phase diagrams were constructed for ME formulations composed of Capmul MCM, Cremophor EL, and propylene glycol. Frovatriptan succinate-loaded ME was optimized by simplex lattice design having the concentration of oil, surfactant, and cosurfactant representing three apex points on the triangle. These were taken as independent variables and percentage drug release as a response variable. All developed batches of ME were characterized for in vitro tests, histopathology study, and pharmacokinetics in Swiss albino rats. Results: Clear MEs were obtained. F5 having particle size – 142.0 nm, zeta potential – 17.7–−7.8 mv, refractive index – 1.38±0.20, drug content – 98.24±0.20%, and drug diffused through dialysis membrane – 85% was the optimized batch. Drug permeation through the nasal mucosa of F5 in the ex vivo study was found to be 82.32%. Histopathology microscopic study has shown that F5 does not cause any irritation and structural changes in sheep nasal mucosa. The pharmacokinetic parameters were determined after nasal and oral administration of F5. For brain tissue, after nasal administration were Cmax181±1.51 ng/ml, Tmax – 2±1.01, area under curve (AUC)0−6 – 390.0±2.08 ng.h/ml. The AUC0−6 attained by nasal ME was 3.29 times greater than oral solution. Drug targeting index of frovatriptan succinate was 2.06. This was found satisfactory. Conclusion: Microemulsion of said composition was found to be enhancing delivery of frovatriptan succinate to brain tissues through nasal route

ACUTE AND SUB-ACUTE ORAL TOXICITY ASSESSMENT OF THE POLYHERBAL FORMULATION IN ALBINO WISTER RATS

Objective: Polyherbal formulation (PHF) is prepared from five herbs; these herbs are well-known and widely used in the traditional system of medicine for the treatment of diabetes and various diseases. Individually, each herb is completely safe, but the combined effects of these herbs are not known. Thus, the main objective of the present study was to assess the toxicological profile of PHF by acute and sub-acute oral toxicity in rats.Methods: The acute and sub-acute oral toxicity study was carried out as per OECD guidelines 423 and 407 respectively. In the acute toxicity study female albino Wistar rats administered single oral dose (2000 mg/kg) of PHF, while in sub-acute toxicity study male and female albino Wistar rats administered daily oral doses (100, 200 and 400 mg/kg) of PHF for 28 d. At the end of the study, the animals were humanely sacrificed and assessed for the effect of PHF on body weight and relative organ weights and hematological, biochemical and histopathological parameters.Results: In the acute toxicity study no mortality or behavioral changes were observed in rats treated with a single dose of PHF (2000 mg/kg) indicating that the LD50 is higher than 2000 mg/kg. In the sub-acute toxicity study, PHF was administered at three dose levels (100, 200 and 400 mg/kg), showed no significant changes in body weight and relative organ weights and hematological, biochemical and histopathological parameters.Conclusion: These results exhibit the absence of acute and sub-acute oral toxicity after treatment of PHF in rats. However, further studies in animals and in humans are needed in order to have sufficient safety evidence for its use in humans.Keywords: Polyherbal formulation, Acute and sub-acute toxicity, Hematology, Biochemistry, Histopatholog

DEVELOPMENT OF METOCLOPRAMIDE HYDROCHLORIDE IN SITU GEL: NASAL DELIVERY AND PHARMACOKINETICS IN NEW ZEALAND RABBITS

Objective: Systemic bioavailability of metoclopramide hydrochloride (MCH) is 32–80% by oral route. The study was targeted to develop in situ gel of MCH for nasal delivery and to study its pharmacokinetics in healthy rabbits. Pre-systemic metabolism can be overcome. Methods: Poloxamer 407 (P407) aqueous solutions were prepared by cold method. In 32 factorial design, independent variables were Carbopol 934P and polyethylene glycol 6000 (PEG 6000), and dependent responses were gelation temperature, mucoadhesive strength, and drug release. A Pharmacokinetic study was carried out in New Zealand rabbits. The optimized in situ gel (1 mg/ml) was compared with marketed Reglan® (2 mg/2 ml) injection. Area under the curve (AUC), Cmax, and Tmax were estimated. Results: F2 was an optimized formulation. The study showed that P407 solutions formed a gel at nasal temperature 34°C having mucoadhesive strength 806.12±3.45 dyne/cm2. MCH release was found to be 93.74±1.31% within 6 h. Histopathological examination of formulation F2 exhibited safety to the nasal mucosa. The pH of formulations was 5.1±0.1 to 5.6±0.1 in the range of pH of nasal cavity. Plasma samples were analyzed by liquid chromatography/mass spectroscopy (LC/MS). The area under curve AUC0-4 for in situ gel by nasal route was 2716±4.617 ng/h/ml and for marketed solution by intravenous route was 2874±1.0816 ng/h/ml. These were comparable. Nasal bioavailability was found 94.50% from in situ gel. Duration of action was longer, and steady-state concentration was found for in situ gel. Conclusion: In situ gel was capable to release MCH in systemic circulation. In vivo study in rabbits has proved the improved bioavailability of MCH administered nasally. The optimized gel preparation was found to be promising for improved bioavailability

DEVELOPMENT AND IN-VITRO EVALUATION OF QUANTUM DOTS AS A CARRIER FOR DELIVERY OF 5-FLUOROURACIL

Objective: The present study was aimed to develop and evaluate quantum dots (QDs) as a carrier for delivery of 5-fluorouracil (5-FU).Methods: This research work includes a synthesis, characterization and in vitro study of 5-fluorouracil (5-FU) QDs. Zinc oxide QDs were synthesized, and the drug was loaded on them. These QDs were further coated with Eudragit E PO to achieve drug release only at the acidic pH range as well as to overcome release of drug in the formulation vehicle itself.Results: For 5-FU QDs optimized batch, yield (74±0.001 %), drug loading (85.58±0.08 %) and drug content (95±0.015%) were observed. FTIR spectroscopy revealed no any incompatibility between drug, polymer and metal SEM images shown drug loaded QDs with rough surface and Eudragit E PO coated QDs with smooth surface. The DSC curve of 5-FU exhibits peak at 286 °C corresponding to its melting point and Eudragit E PO coated QDs exhibit peak at 272 °C. This shifting of the endotherm suggested possible interaction of 5-FU and Eudragit E PO coated QDs. The diffractogram of pure drug showed multi-crystalline nature. However pure Eudragit E PO showed amorphous nature. Optimized QDs showed the crystalline nature of the drug. Mean particle size of optimized formulation batch was 201.92 nm and zeta potential was found+1.85 mV.Conclusion: An Optimized batch of QDs has the potential to utilize in future for imaging of cancer cells and targeting delivery of 5-FU.Â

Scattering Behaviour of Saline Soils from Gujarat State at 5.3 GHz Frequency

ABSTRACT: This study presents experimental measurements of complex dielectric constant at C-band microwave frequency of dry and moist saline soils collected from Dandi (Dist. Navsari) site of Gujarat state (India). An automated microwave set-up tuned at 5.3 GHz frequency is used for this purpose. Measured values of dielectric constant are then used to estimate the scattering coefficient by using perturbation model. Our results indicate relatively lower rate of increase in ε' and order of magnitude higher values of ε'' for these saline soils when their gravimetric MC is changed from 10 to 30% than that reported for non-saline soils by earlier researchers. Further, at constant value of MC, scattering coefficient of soil sample also increases with increase in the incident angle for vertical polarization, and this increase continues up to angles between 60 o to 70 o , at which it reaches maximum value and beyond this, it decreases sharply. Further, for vertical and horizontal polarizations, at constant value of incident angle, our results indicate relatively lower rate of increase in scattering coefficient values for saline soils than reported earlier for non-saline soils when gravimetric MC is changed from 10 to 20%. This data is very useful in understanding dielectric behaviour of saline soils and also for designing the active sensors for these soils

Effect of some non-genetic factors on productive and reproductive traits of Mehsana buffaloes

The records of 7782 Mehsana buffaloes sired by 184 sires maintained at Dudhsagar Research and Development Association (DURDA), Dudhsagar Dairy, Mehsana, Gujarat born during 1989 to 2012 were collected and analysed to examine the effect of non-genetic factors viz. period and season of calving and age at first calving. The least squares analysis was used for estimation of various non-genetic factors on First Lactation Milk Yield (FLMY), First Lactation Fat Yield (FLFY), Average Fat Percentage (AFP) and Age at First Calving (AFC). The least squares mean with standard error of FLMY, FLMY, AFP and AFC were estimated to be 1900.68±7.65 lit., 135.04±0.57 kg, 7.11±0.11 percentage and 1407.18±4.36 days, respectively. Highly significant (P≤0.01) effect of all the non-genetic factors (period and season of calving and age at first alving group) under study was observed on FLMY, FLMY and AFP in Mehsana buffaloes. Further, highly significant (P≤0.01) effect of season and period of birth was recorded on AFC. It is worthy to note that in Mehsana breed evaluation programme these factors should be considered as they have great influence of them

Overcoming Poor Solubility of Dimenhydrinate: Development, Optimization and Evaluation of Fast Dissolving Oral Film

Purpose: To develop fast dissolving oral film to address vomiting and nausea in pediatric population. Methods: Oral films of Dimenhydrinate were prepared by solvent casting method by using hydroxypropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 400 (PEG 400) and croscarmellose sodium. Solubility of dimenhydrinate was enhanced by ethanol as a co-solvent. To make dimenhydrinate palatable sodium saccharin and peppermint oil were used. All films were evaluated for mechanical parameters, surface pH, morphology, disintegration time and percent dissolution. Results: Films were smooth, acceptable and white in colour. For optimized batch, drug content (99.106%), disintegration time (25 sec), dissolution (99.10% in 210 sec), surface pH (6.81) were acceptable. Conclusion: Optimized batch, due to its potential to deliver through fast dissolving film, can be developed for clinical use

Test-day and other milk recording options for prediction of lactation milk yield in Jaffarabadi (Bubalus bubalis) buffaloes

Generally, standard lactation milk yield is predicted based on test-day records collected at monthly intervals. Test-day milk production at different time intervals other than monthly intervals can be used to predict lactation milk yield of field bovines in field conditions. With the same possibility, this study was carried out to predict lactation milk yield in Jaffarabadi buffaloes from various test-day milk yield data retrieved for different time intervals. A total of 1,15,339 daily milk yield records in 176 lactations of 1st to 6th parity of 30 Jaffarabadi buffaloes lactating at the Cattle Breeding Farm, Kamdhenu University, Junagadh, Gujarat over a period of 28 years (1991 to 2018) were used for the study. Single monthly test-day milk yield recorded on 125th, 155th or 185th day i.e., 5th, 6th and 7th monthly test day yield alone provided only 50% reliability in determining the standard lactation milk yield. Daily peak yield alone was also found to be a poor predictor for lactation yield. Prediction equations using combination of consecutive two monthly test day yields from 4th to 10th monthly test day were found reliable source for prediction of lactation milk yield providing accuracy up to 82.19% whereas, daily peak yield in combination with single monthly test day yield at mid and late lactation was also predicted lactation milk yield with accuracies up to 72.23%. Milk production recorded at weekly interval could also be used to approximate milk production using the equation 15.35+6.91 × Sum of all weekly test-day yields, with precision of 98.93% or milk production recorded at fortnightly interval by the equation 18.04+14.65 × Sum of fortnightly test-day yields, with precision of 97.14%. &nbsp

Development and validation of a spectrofluorimetric method for the estimation of camptothecin in bulk and formulation

A simple, accurate, precise, sensitive and cost-effective spectrofluorimetric method was developed and validated for the estimation of Camptothecin (CMPTO) in bulk and formulation. The relative fluorescence intensity of Camptothecin was measured in distilled water at an excitation wavelength of 278 nm and an emission wavelength of 419 nm. Proposed method was found to be linear over the range of 50 to 3000 ng/ml with correlation coefficient 0.9999. Proposed method was validated using different analytical method validation parameters viz. accuracy, precision, LOD, LOQ, robustness and ruggedness using QC standards as per the ICH guidelines. Thepercentage recovery was found to be 100.64 % and percentage RSD values were found to be less than 2 for accuracy and precision studies. The detection and quantification limits for the proposed method were found to be 15.76 and 47.98 ng/ml, respectively. A simple, accurate, precise, sensitive yet cost-effective spectrofluorimetric method was developed for the estimation of CMPTO in bulk and formulation. The said spectrofluorimetric method was found to be economic as it comprises water as a solvent. Keywords: Spectrofluorimetry, Camptothecin, Validation, Excitation, Emissio

Graphene Quantum Dots Incorporated UiO-66-NH2 Based Fluorescent Nanocomposite for Highly Sensitive Detection of Quercetin

Quercetin can help with a variety of health problems. Most methods for measuring quercetin in biological fluids are characterized by low sensitivity and selectivity. The employment of metal–organic frameworks in sensor applications with carbon-based materials ushers in a new era. In this study, blue fluorescent graphene quantum dots (GQDs) embedded in a UiO-66-NH2 metal–organic framework-based nanoprobe (GQDs@UiO-66-NH2) were constructed for quercetin sensing. Initially, maize husk was used to produce blue fluorescent GQDs, whereas zirconium tetrachloride and 2-aminoterephthalic acid were used to synthesize extremely luminous UiO-66-NH2. The addition of quercetin to GQDs@UiO-66-NH2 leads to fluorescence dampening due to the adsorption potential of UiO-66-NH2. The complexation of zirconium ions with the 3-OH and 4-C＝O functionalities of quercetin resulted in fluorescence quenching. The sensor has a linear concentration range and limit of detection for quercetin of 50–500 and 2.82 ng/mL, respectively. The nanoprobe’s usefulness for quercetin detection was then validated by a selectivity investigation in the presence of interfering chemicals. Furthermore, the percentage relative standard deviations were 4.20% and 2.90%, respectively, indicating great stability and repeatability. Fluorescence “Turn-On–Off” nanoprobes provide a simple, quick, sensitive, and selective method for monitoring quercetin