Saima Amin

Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system.

The present study deals with the development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble third generation calcium channel blocker lercanidipine (LER). Solubility of the LER was estimated in various oils, cosurfactants and surfactants which were grouped into two different combinations to construct pseudoternary phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations from phase diagram. After constructing phase diagram of two different combinations NL-I and NL-II, the effect of cosurfactants on the nanoemulsifying area was studied and the effect of number and length of hydrophobic alkyl chains of cosurfactant in its emulsification capacity was proved. Percentage transmittance, emulsification time, viscosity and droplet size analysis were used to characterize optimized formulations. The optimized formulation composed of Cremophor EL (45% wt/wt), (13.5% wt/wt) Caproyl 90 with (1.5% wt/wt) Transcutol® HP as per limits of inactive ingredients guidelines of FDA and Maisine oil (10% wt/wt). The mean droplet size in selected nanocarrier system was 20.01 nm. The in vitro dissolution profile of LER SNEDDS was found significant in comparison to the marketed LER (Zanidip) tablet and pure drug in pH 1.2, 4.5 and 6.8 buffers. Empty hard gelatin capsule shells were filled using Pfizers Licap technology and charged on stability conditions of 30 °C/65% RH, 40 °C/65%RH and 50 °C/75% in glass bottles where no significant degradation (p>0.05) was observed in 3 months. The results indicate that SNEDDS of LER, owing to nanosized, has potential to enhance the absorption of drug.

Formulation of Self-Nanoemulsifying Drug Delivery System for Telmisartan with Improved Dissolution and Oral Bioavailability

To improve the dissolution and oral absorption of poorly water soluble drug-telmisartan, a self-nanoemulsifying system (SNES) was developed, characterized, and its relative bioavailability was compared to commercially available formulation. Safsol-218, Tween-20, and Transcutol P were chosen as oil, surfactants, and cosurfactants respectively as they show highest solubility for telmisartan. The solubility of drug was further improved by adding sodium hydroxide (0.67%). The droplet size of the optimized emulsion was also evaluated and was observed to be in nano range. The dissolution of drug was rapid in simulated gastric fluid (pH 1.2) as well as in simulated intestinal fluid (pH 6.8) and was found to be pH independent. The pharmacokinetic parameters (AUC0→t ± SD, Cmax, and Tmax) of optimized formulation of telmisartan after oral administration as SNES were compared with oral tablet and API suspension of drug. The results showed a 4.34-fold increase in oral bioavailability of drug in comparison to tablet. The results demonstrate that SNES composed of Sefsol-218, Tween-20, and Transcutol P substantially enhanced the bioavailability of telmisartan. Further, it showed highly significant fall (p < 0.001) in mean blood pressure of hypertensive rats for 48 hours. Thus, our study provides a useful oral dosage form for telmisartan.

Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics

Abstract Cancer has been growing nowadays consequently high number of death ascertained worldwide. The medical intervention involves chemotherapy, radiation therapy and surgical removal. This conventional technique lacking targeting potential and harm the normal cells. In drug treatment regimen, the combination therapy is preferred than single drug treatment module due to higher internalization of chemotherapeutics in the cancer cells both by enhance permeation retention effect and by direct cell apoptosis. The cancer therapeutics involves different methodologies of delivering active moiety to the target site. The active and passive transport mode of chemotherapeutic targeting utilizes advance nanocarriers. The nanotechnological strategic treatment applying advance nanocarrier greatly helps in mitigating the cancer prevalence. The nanocarrier-incorporating nanodrug directed for specific area appealed scientist across the globe and issues to be addressed in this regard. Therefore, various techniques and approaches invented to meet the objectives. With the advances in nanomedicine and drug delivery, this review briefly focused on various modes of nanodrug delivery including nanoparticles, liposomes, dendrimer, quantum dots, carbon nanotubes, metallic nanoparticles, nanolipid carrier (NLC), gold nanoshell, nanosize cantilevers and nanowire that looks promising and generates a novel horizon in cancer therapeutics.

A study of the chemical composition of black cumin oil and its effect on penetration enhancement from transdermal formulations.

The chemical composition of the solvent extracted fixed oil of black cumin (Nigella sativa L.) seeds was determined by capillary GC and GC/MS. Thirty-two fatty acids (99.9%) have been identified in the fixed oil. The major fatty acids were linoleic acid (50.2%), oleic acid (19.9%), margaric acid (10.3%), cis-11,14-eicosadienoic acid (7.7%) and stearic acid (2.5%). The effect of black cumin oil on in vitro percutaneous absorption of the model lipophilic drug carvedilol was investigated using excised rat abdominal skin. Transdermal flux, permeability coefficient and enhancement factor were calculated for different concentrations of oil in isopropyl alcohol. Black cumin oil (5% v/v) exhibited the highest enhancement in permeation. The increase in the permeability of the drug is due to increased drug diffusivity through the stratum corneum under the influence of black cumin oil. A higher content of linoleic acid (and other unsaturated fatty acids) in the oil has been postulated to be responsible for the enhancement of in vitro percutaneous absorption of the drug.

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF DICLOFENAC DIETHYLAMINE AND CURCUMIN IN TRANSDERMAL GELS

A reversed phase high performance liquid chromatographic (RP-HPLC) method using Symmetry C18, 5.0-µm column was developed for simultaneous determination of Diclofenac diethylamine (DDEA) and Curcumin (CRM). Mobile phase consisted of orthophosphoric acid 0.1% and acetonitrile (65:35), and the flow rate was 1.5 mL/min and elution was monitored initially at 425 nm for CRM, after 14.7 min wavelength was changed to 275 nm for detection of DDEA. Response was a linear function of concentration over the range 0.245–1.96 µg/mL (R2 = 0.9998) for DDEA and 55–445 ng/mL (R2 = 0.9992) for CRM and the limits of detection were 245.5 ng/mL for DDEA and 55.30 ng/mL for CRM. The limit of quantitation was 491.1 ng mL − 1 for DDEA and 165.87 ng mL − 1 for CRM. The method was validated in accordance with ICH guidelines. The method was used for simultaneous quantification of DDEA and CRM in transdermal gel formulations and to check content uniformity. The excipients present in the formulation did not interfere with the assay. The method is suitable for application in quality-control laboratories, because it is simple and rapid with good accuracy and precision.

Development, Characterization, and Pharmacodynamic Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems

The objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo performance. The research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along with in vitro dissolution and in vivo pharmacodynamic profiling. Based on dissolution profile, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5%u2009w/w), Transcutol P (12.7%u2009w/w), and HCT (4.17%u2009w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT.

The solution, solid state stability and kinetic investigation in degradation studies of lercanidipine: study of excipients compatibility of lercanidipine

The objectives of this research were to evaluate the stability of lercanidipine in solution state and solid state and explore the compatibility of drug with oils, surfactants and cosurfactants as excipients. The effect of pH on the degradation in solution state was studied through pH-rate profile of lercanidipine in constant ionic strength buffer solutions in pH range 1–8 which gives the pH of maximum stability. Powdered lercanidipine was stored under 40°C/0%~75% relative humidities (RH) or 0% RH/5~50°C to study the influence of RH and temperature on the stability of lercanidipine in solid state. Binary mixtures of lercanidipine and different excipients were stored at 40°C/75% RH, 40°C and at room temperature for excipient compatibility evaluation. The degradation of lercanidipine at different pH appears to fit a typical first-order reaction, but in solid state, it does not fit any obvious reaction model. Moisture content and temperature both play important roles affecting the degradation rate. Lercanidipine exhibits good compatibility with surfactants, cosurfactants and oils as excipients under stressed conditions of different storage temperature in a 3-week screening study. Moreover, the proposed high-performance liquid chromatography method was utilized to investigate the kinetics of the acidic and alkaline degradation processes of lercanidipine at different temperatures.

In vitro characterization and pharmacodynamic evaluation of furosemide loaded self nano emulsifying drug delivery systems (SNEDDS)

Poor water solubility is one of the reasons for erratic absorption after oral administration of furosemide (FSM), an antihypertensive loop diuretic. Self nano emulsifying drug delivery system (SNEDDS) is a novel drug delivery system utilized to improve the water solubility, permeability and ultimately bioavailability. FSM solubility was determined in various vehicles oils, surfactants and co surfactants. Self emulsification region for the rational design of SNEDDS formulations were identified by pseudoternary diagrams. Developed formulations were characterized by zeta potential determination, droplet size analysis, dilution test, viscosity determination, in vitro dissolution studies and in vivo pharmacodynamic evaluation. A remarkable increase in dissolution was observed for the optimized SNEDDS when compared with the plain FSM and marketed formulation by in vitro dissolution studies. The pharmacological effect of FSM was improved by SNEDDS formulation as compared to plain FSM. The study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of FSM to improve its bioavailability.

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR ANALYSIS OF LERCANIDIPINE IN BULK DRUG AND MICROEMULSION FORMULATION

A simple, sensitive, and stability indicating method is described for the quantitative determination of lercanidipine both in bulk drugs and microemulsions, also in the presence of its degradation products. The method was based on high-performance liquid chromatographic (HPLC) separation of drug from its degradation products. The analysis was carried out on C18 reverse phase (Agilent TC-C18(2) column (250 mm × 4.6 mm I.D., 5-micron particle size)) in isocratic mode at ambient temperature using separation mobile phase, impelled by binary pump, consisting of acetonitrile (ACN) and disodium hydrogen phosphate (Na2HPO4) buffer, pH 4 (55:45, v/v volume). Flow rate was 1.0 mL min−1 with an average operating pressure of 140 kg cm−2 and tR was found to be 8.3 ± 0.15 min. Quantitation was achieved with UV detection at 240 nm based on peak area with linear calibration curves at concentration range 10–40 µg mL−1. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines. The wide linearity range, sensitivity, accuracy, and simple mobile phase imply the method is suitable for routine quantification of lercanidipine in bulk drugs and microemulsion formulation with high precision and accuracy.

Rapid preparative isolation of erythrocentaurin from Enicostemma littorale by medium‐pressure liquid chromatography, its estimation by high‐pressure thin‐layer chromatography, and its α‐amylase inhibitory activity

Erythrocentaurin is a relatively simple natural product present among the members of Gentianaceae. A preparative method for the isolation of erythrocentaurin from the ethyl acetate fraction of Enicostemma littorale using medium-pressure liquid chromatography has been reported. The method consisted of a simple step gradient from 10 to 20% ethyl acetate in n-hexane. Using a 70 × 460 mm Si60 column, this method is capable of processing 20 g of material in <3 h (purity ≈ 97%). The recovery of erythrocentaurin was 87.77%. Estimation of erythrocentaurin in extracts and fractions based on high-pressure thin-layer chromatography was carried out on silica gel 60 F(254) plates with toluene/ethyl acetate/formic acid (80:18:2 v/v/v) as the mobile phase. The densitometric analysis was performed at 230 nm. A well-separated compact band of erythrocentaurin appeared at R(f )0.54 ± 0.04. The analytical method showed good linearity in the concentration range of 200-1500 ng/band with a correlation coefficient of 0.99417. The limits of detection and quantification were found to be ≈60 and ≈180 ng/band, respectively. Erythrocentaurin exhibited a concentration-dependent α-amylase inhibition (IC(50) 1.67 ± 0.28 mg/mL). The outcome of the study should be considered for pharmacokinetic and biotransformation studies involving E. littorale.