Self-emulsification Time Research Articles

PREPARATION, CHARACTERIZATION AND STABILITY STUDIES OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF NIFEDIPINE

Objective: The objective of this work was to improve the solubility and dissolution rate of Nifedipine by preparing a solid-self micro emulsifying drug delivery system (Solid-smedds).
 Methods: Liquid-self-emulsifying drug delivery system formulations were prepared by using linseed oil as oil, tween 80 as a surfactant and PEG 400 as cosurfactant. Components were selected by solubility screening studies and the self-emulsifying region was identified by the pseudo-ternary phase diagram. Thermodynamic stability study was performed for the determination of stable liquid-smedds formulation. These formulations were evaluated for self-emulsification time, drug content analysis, robustness to dilution test, particle size analysis, in vitro diffusion study, and Stability study. Solid self-micro emulsifying formulations were prepared by using aerosil-200 at a different ratio. Lf9S (0.65:1) was selected due to its highest drug entrapment efficiency and a decrease in particle size. It was selected for further studies into DSC, SEM, FTIR, and XRD analysis.
 Results: DSC and XRD result shows that the drug within the formulation was in the amorphous state. From the SEM study, it was observed that the drug has been uniformly distributed and having a smooth surface. From the in vitro dissolution study, it improved the dissolution rate of nifedipine which was 98.70% of drug release where pure drug release only 6.72%.
 Conclusion: In conclusion, a solid self-micro emulsifying drug delivery system is improved the solubility and drug release rate but also improved the stability of the formulation.

Formulation and evaluation of solid self-microemulsifying drug delivery system for azilsartan medoxomil

This study aimed to develop solid self-microemulsifying drug delivery system (S-SMEDDS) for solubility enhancement of azilsartan medoxomil (AZL). Ternary phase diagrams were constructed using surfactant: co-surfactant at 1:0, 1:1, 1:2 and 2:1 ratios. Initially, the oils, surfactants and co-surfactants were screened. The drug–soya lecithin complexes were prepared and characterized for complexation percentage, complex solubility, and partition coefficient. The liquid SMEDDS were prepared and evaluated for thermodynamic stability, self-emulsification efficiency and time, viscosity, size and polydispersibility index, zeta potential, drug loading, and in vitro dissolution. Further, the solid SMEDDS were formulated and evaluated for morphological characterization, and thermal behavior. The solid SMEDDS were filled with hard gelatin capsule and accessed for in vitro drug release profile. S-SMEDDS containing Syloid® XDP 3150 had highest adsorption capacity. Self-emulsification time, drug loading and percentage transmittance were 25 ± 1.23 s, 99.20 ± 0.11% and 99.3 ± 0.1%, respectively. Particle size, polydispersibility index and zeta potential were 201.0 nm, 0.544 and -19.7 mV, respectively. S-SMEDDS had good flow property, spontaneous self-microemulsification property and improved in vitro dissolution profile of AZL when compared to pure AZL.

Preparation of self micro emulsifying drug delivery system(smedds) of poorly soluble drug eprosartan mesylate and its in vitro evaluation

Eprosartan Mesylate (EM), an angiotensin II receptor blocker used in the treatment of high blood pressure. But poor solubility and bioavailability (13%) of eprosartan mesylate is a major challenging factor for improving its drug release rate. The main objective of the present work to develop and characterize self micro emulsifying drug delivery system of eprosartan mesylate by using compatible oil, surfactant and co-surfactant. For the selection of oil, surfactant and cosurfactant, solubility screening studies has been carried out. The nine formulations are prepared using peppermint oil, tween 80 and PEG 400. A pseudo ternary phase diagram was prepared to determine the self emulsion region. Four optimized formulations were prepared at 1:1 ratio(a mixture of surfactant and cosurfactant). These four formulations were evaluated for self-emulsification time, droplet size measurement, drug content analysis robustness to dilution test, viscosity analysis, f.t.i.r. The study and in-vitro diffusion studies. The ratio of scosmix (a mixture of surfactant and cosurfactant) of optimized formulation (pf5) was varied to pfa1 (2:1), pf2 (3:1), pfa3 (1:2) and compared with pure drug. The formulation having pfa1 (2:1) shown drug release of 93.13 % in 330 minutes where as pure drug showed a drug release of 54.51% in 330 minutes. So the prepared SMEDDS formulations were efficient and better than the pure drug, and it followed Korsmeyer pappes due to highest r2 value followed by Hixon crowel. It was concluded that incorporation of eprosartan mesylate in selfmicroemulsifying system is a great potential for improving the solubility and dissolution rate of eprosartan mesylate.

Diseño y desarrollo de un sistema de entrega de fármaco autoemulsificable líquido de ibuprofeno incorporado por el método de adsorción por portador en una forma farmacéutica sólida (comprimidos)

El ibuprofeno es uno de los fármacos más utilizados e indicado para terapias antiinflamatorias, dolor, entre otras patologías. Sin embargo, este fármaco presenta una baja y errática biodisponibilidad, debido a la pobre solubilidad acuosa intrínseca del mismo, por lo cual esta categorizado como clase II en el sistema de clasificación biofarmacéutica. El objetivo de este trabajo fue desarrollar, diseñar y evaluar un sistema de entrega de fármaco autoemulsificable (SEDDS) para mejorar la solubilidad y velocidad de disolución de ibuprofeno.Aceites, cosolventes, tensioactivos y portadores porosos fueron evaluados por su capacidad de mejorar la solubilidad del ibuprofeno, habilidad de autoemulsificación, robustez en diferentes pH y capacidad de adsorción. El aceite de coco, Tween 80 y propilenglicol lograron un aumento significativo de la solubilidad acuosa del ibuprofeno en un tiempo de autoemulsificación menor a 2 minutos. Neusilin US2® fue seleccionado como portador, dando como resultado un pequeño granulo de excelente fluidez, que permitió obtener comprimidos que cumplieron satisfactoriamente las pruebas de control de acuerdo con las especificaciones establecidas. Los SEDDS líquidos y sólidos son una alternativa de formulación ventajosa y prometedora para mejorar la solubilidad de fármacos pobremente solubles de acuerdo con el sistema de clasificación biofarmacéutica, a través de sus propiedades de solubilización.

Design and Evaluation of a Self-Emulsifying Drug Delivery System of Aripiprazole

The present investigation is aimed at enhancing the solubility and the dissolution rate of aripiprazole by formulating a self-micro emulsifying drug delivery system. The preliminary solubility screening of aripiprazole was determined in oils, surfactants and cosurfactants, respectively. Among those screened, isopropyl myristate, Tween 80 and propylene glycol showed good solubilizing efficiency and were selected for further formulations. A pseudoternary phase diagram was constructed at the ratios of 2:1, 3:1, 4:1 of oil to Smix (surfactant:Tween 80) and cosurfactant (propylene glycol) to find out the self-emulsification region. In vitro dissolution studies of the formulations were carried out in a simulated acidic buffer pH 2.2. A liquid self-micro emulsifying drug delivery system with an optimum composition was converted to solid formulation using crospovidone. Both solid and liquid formulations were evaluated for the cloud point and self-emulsification time. Differential scanning calorimetry endotherm provided confirmation for the amorphisation of the drug. Zeta potential and particle size analysis was carried out on the optimized formula. These studies revealed that the prepared self-micro emulsifying drug delivery system exhibited increased dissolution rate profile in comparison to the pure drug and marketed aripiprazole tablets.

Novel Combination for Self-Nanoemulsifying Drug Delivery System of Candesartan Cilexetil

Solubility problem of many of effective pharmaceutical molecules are still one of the major obstacle in theformulation of such molecules. Candesartan cilexetil (CC) is angiotensin II receptor antagonist with very low water solubility and this result in low and variable bioavailability. Self- emulsifying drug delivery system (SEDDS) showed promising result in overcoming solubility problem of many drug molecules. CC was prepared as SEDDS by using novel combination of two surfactants (tween 80 and cremophore EL) and tetraglycol as cosurfactant, in addition to the use of triacetin as oil. Different tests were performed in order to confirm the stability of the final product which includes thermodynamic study, determination of self-emulsification time, particle size and zeta potential measurement, and in-vitro drug release. The results showed that the particle size of the best formula was 13.3 nm and zeta potential of -37.45 mV with approximately 100% release after 45 minutes .These results suggest that the preparation of CC. as SEDDS with the use of the above combination of surfactant and cosurfactant is a promising maneuver for oral delivery of CC. in order to improve its bioavailability.

In vitro characterization of statistically optimized quetiapine-loaded self-nanoemulsified systems with quality by design

Objective: To optimize and characterize quetiapine (QP)-loaded self-nanoemulsified drug delivery systems (SNEDDS) by 3-factorial 3-level Box–Behnken design (BBD) to improve the dissolution. Methods: Amounts of olive oil (X 1 ), tween 80 (X 2 ), and PEG 400 (X 3 ) as independent factors, whereas % limpidity (Y1), self-emulsification time (SET) (Y2), and drug released at 15 min (T 15 ) (Y3) as responses were employed in BBD. Three-dimensional response surface plots were run to understand the main interaction and quadratic effects of independent variables. Preliminary screening was carried out by equilibrium solubility and emulsification efficiency studies. Nanoemulsification region was recognized by pseudoternary plot. Results: Mean droplet size of optimized nanodispersion was 89.68 nm, electrokinetic potential was −27.2 mV and polydispersity index 15 . Software-generated model graphs (predicted versus actual and residual versus predicted) for all three responses were produced without outliers and thus indicated the adequacy of selected statistical model. Conclusion: This study explained the effectiveness of BBD in insights of formulation variables and quality of QP-loaded nanoemulsified systems so as to enhance dissolution. As a result, BBD was a well-suitable experimental design in predicting the responses of QP-loaded liquid SNEDDS.

Olmesartan Medoxomil-Loaded Self-Nanoemulsifying Drug Delivery Systems: Design, In-Vitro Characterization, and Pharmacokinetic Assessments in Rabbits Via LC-MS/MS

Olmesartan medoxomil (OLM) is a lipophilic (log P = 4.31) antihypertensive drug suffering from limited oral bioavailability in humans (26%) due to its low aqueous solubility, uncontrolled enzymatic conversion to the active metabolite (olmesartan; OL) and efflux by drug resistance pumps. Surmounting such limitations via incorporation of OLM into self-nanoemulsifying drug delivery systems (SNEDDS). Based on OLM-equilibrium solubility studies in various oils, surfactants and co-surfactants, Capmul® MCM, Tween® 20, Cremophor® EL and polyethylene glycol-400 (PEG) were combined in different ratios to plot ternary phase diagrams. OLM-loaded SENDDS were developed and evaluated for particle size, polydispersity index (PDI), zeta potential, self-emulsification time, morphology, drug released percentages after 5-min (Q5min%), 1-hour (Q1h%) and dissolution efficiency percentages (DE1h%). The OL pharmacokinetics from SNEDDS (F6) and Benicar® tablets were evaluated (LC-MS/MS) in rabbits. Spherical OLM-loaded SNEDDS were developed. The best-achieved SNEDDS (F6) showed short emulsification time (13 s), fine droplet size (60.00 nm), low PDI (0.25), negative zeta potential (-14.4 mV), promising dissolution parameters; Q5min% (29.78%), Q1h% (66.69%) and DE1h%(47.96%) and enhanced in vivo absorption characteristics; shorter Tmax, higher Cmax and larger AUC(0−48h; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM.

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.Results: The optimum formulations were composed of different ratios of Capryol™ 90 as an oil phase, Cremophor® RH40 as a surfactant, and Transcutol® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and emulsification time not exceeding 1 min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.

Self-Nanoemulsifying Drug Delivery Systems of Poorly Soluble Drug Dutasteride: Formulation and In-Vitro characterization

The present study aims to prepare and evaluate the self-nanoemulsifying drug delivery (SNEDDS) system to enhance dissolution rate of a poorly soluble drug dutasteride. The formulation was prepared using capryol PGMC, Cremophor EL, and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to find out the nanoemulsification range and also to evaluate the effect of dutasteride on the emulsification behavior of the phases. Prepared SNEDDS formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self-emulsification time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The particle size, zeta potential and polydispersity index of the optimized formulation found to be 35.45 nm, -15.45 and 0.19, respectively. The in vitro results are revealed that the prepared formulation enhanced the dissolution rate of dutasteride significantly as compared with pure drug. Based the results, it was concluded that the dutasteride-loaded SNEDDS shows potential to enhance the dissolution of dutasteride, thus improving the bioavailability and therapeutic effects.

Lipid-based nanosystem of edaravone: development, optimization, characterization and in vitro/in vivo evaluation

Edaravone (EDR) is a well-recognized lipophilic free radical scavenger for diseases including neurodegenerative disease, cardiovascular disease, and cancer. However, its oral use is restricted due to poor oral bioavailability (BA). The aim of present research was to enable its oral use by developing a lipid-based nanosystem (LNS). The components of LNS including oil, surfactants, and co-surfactants were selected based on their potential to maximize the solubilization in gastrointestinal (GI) fluids, reduce its glucuronidation and improve transmembrane permeability. The liquid LNS (L-LNS) with Capryol™ PGMC (Oil), Cremophor® RH 40:Labrasol®:TPGS 1000 (1:0.8:0.2) (Surfactant) and Transcutol P® (Co-surfactant) were optimized to form microemulsion having droplet size (16.25 nm), polydispersity index (0.039), % Transmittance (99.85%), and self-emulsification time (32 s). It significantly improved the EDR loading as well as its metabolism and permeability profile during transport across the GI tract. To overcome the possible drawbacks of L-LNS, Aerosil® 200 was used to formulate solid LNS (S-LNS), and its concentration was optimized based on flow properties. S-LNS possessed all quality attributes of L-LNS confirmed by solid-state characterization, reconstitution ability, and stability study. The dissolution rate of EDR was significantly enhanced with L-LNS and S-LNS in simulated gastric, and intestinal fluids. The pharmacokinetic study revealed significant improvement in relative BA, Cmax, and t1/2 with L-LNS and S-LNS against EDR suspension. Moreover, S-LNS showed superior cellular uptake and neuroprotective effect compared to EDR in SH-SY5Y695 cell line. An appropriate selection of the components of LNS could enable effective oral delivery of challenging therapeutics that are conventionally used by the parenteral administration.

Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model

Purpose. Oxidative stress is the leading cause in the pathogenesis of Parkinson’s disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. Methods. In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box–Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson’s-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. Results. An optimized SNEDDS formulation consisting of Sefsol + vitamin E–Solutol HS 15–Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. Conclusion. Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in neurodegenerative disorders like Parkinson’s disease.

Development and Evaluation of Liquid and Solid Self-microemulsifying Drug Delivery System of Lovastatin

Aim: The present investigations was aimed to improve the solubility, dissolution rate and ultimately the bioavailability of a poorly water soluble BCS class II drug Lovastatin, by formulating it as self-microemulsifying drug delivery system (SMEDDS). Materials and Methods: Liquid SMEDDS of the drug were formulated using Labrafil M 1944, Acrysol EL 135 and Lauroglycol as oil, surfactant and co-surfactant respectively. The prepared systems were characterized for self-emulsification time, robustness to dilution, % transmittance, globule size and thermodynamic stability. Ternary phase diagrams were plotted to identify the area of microemulsification. The optimized liquid SMEDDS was transformed into free flowing powder using Neusilin US2 as the adsorbent. Results and Discussion: Self microemulsifying powder retained the self microemulsifying property of the liquid SMEDDS. Differential scanning calorimetric and X-ray powder diffraction studies confirmed solubilization of the drug in the lipid excipients and or transformation of crystalline form of the drug to amorphous one in solid-SMEDDS. This was supported by scanning electron microscopy studies which did not show evidence of precipitation of drug on the surface of the carrier. In-vitro dissolution studies revealed enhanced release of the drug from solid-SMEDDS as compared to pure drug and the marketed formulation. Similarly the in-vitro absorption studies revealed significant enhancement in drug release from the SMEDDS as compared to plain drug suspension. Conclusion: It can be concluded that the SMEDDS formulation of Lovastatin has the potential of improved delivery of the lipophilic drug and is amenable to development of solid dosage form using Neusilin US2 as the porous carrier.

Formulation optimization of aprepitant microemulsion-loaded silicated corn fiber gum particles for enhanced bioavailability

The present investigation was aimed at development of silicate corn fiber gum (SCFG) particles as superior solid carrier for the preparation of Aprepitant (APT)-loaded self-emulsifying powder (SEP) system. 24 D-optimal mixture design with three level process variables was employed to develop SCFG particles, utilizing flow descriptors and hydrophobicity descriptors as response variables. The results indicated that blending of CFG (51.4% w/w) and magnesium silicate (MS) (48.6% w/w) using freeze-drying technique was found to have highest desirability (0.904). The developed SEP showed highest oil desorbing capacity, low self-emulsification time and highest drug content. It was observed that SCFG-SEP (F2 formulation) showed lowest PDI (0.2445 ± 0.03) as well as smallest particle size (127 ± 5.8 nm). The droplets were uniform and maintain their integrity after reconstitution (TEM analysis). Furthermore, APT-loaded SEP showed enhanced in vitro dissolution (4 folds) and ex vivo performance (7-fold enhanced Papp) as compared to pure APT. Furthermore, in vivo pharmacokinetic study showed that significant enhancement (p > 0.05) in Cmax was evident with APT-loaded F2 (SCFG-SEP) (1.93-fold) and F4 (Aerosil 200-SEP) (1.58-fold). The data also suggested increase in absorption rate when APT incorporated into SCFG-SEP. Thus, findings pointed toward enhanced bioavailability of APT when loaded into SCFG particles. Overall, the developed SCFG particles could be considered as a better alternative to already available solid carrier(s).

Enhanced oral bioavailability of lurasidone by self-nanoemulsifying drug delivery system in fasted state

Objective: The purpose of this work was to develop a new formulation to enhance the bioavailability and reduce the food effect of lurasidone using self-nanoemulsifying drug delivery systems (SNEDDSs).Methods: The formulation of lurasidone-SNEDDS was selected by the solubility and pseudo-ternary phase diagram studies. The prepared lurasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis, zeta potential and in vitro drug release. Lurasidone-SNEDDSs were administered to beagle dogs in fed and fasted state and their pharmacokinetics were compared to commercial available tablet as a control.Results: The result showed lurasidone-SNEDDS was successfully prepared using Capmul MCM, Tween 80 and glycerol as oil phase, surfactant and co-surfactant, respectively. In vitro drug release studies indicated that the lurasidone-SNEDDS showed improved drug release profiles and the release behavior was not affected by the medium pH with total drug release of over 90% within 5 min. Pharmacokinetic study showed that the AUC(0–∞) and Cmax for lurasidone-SNEDDS are similar in the fasted and fed state, indicating essentially there is no food effect on the drug absorption.Conclusion: It was concluded that enhanced bioavailability and no food effect of lurasidone had been achieved by using SNEDDS.

Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization

Context: Docosahexanoic acid (DHA) is an essential omega-3 fatty acid for normal brain development and its use has increased considerably in recent years.Objective: The aim of this study is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of DHA for improved palatability, dispersibility and bioavailability.Methods: The SNEDDS were prepared and evaluated for miscibility, employing different combinations of olive oil and soyabean oil as oil phase, Span 80, Span 20, soya phosphatidylcholine, Labrafil M 1944 CS as surfactants while Tween 80, PEG 400, Cremophor RH40 and propylene glycol as cosurfactants. Thermodynamically stable SNEDDS were characterized for dispersibility, self-emulsification time, droplet size, zeta potential along with sensory analysis. The optimized formulation was subjected to ex vivo and in vivo evaluation such as intestinal permeability, memory performance test, brain concentration and histopathology studies.Results: The optimized SNEDDS formulation showed emulsification time of 27 ± 4.7 s with droplet size of 17.6 ± 3.5 nm and zeta potential of −37.6 ± 0.5 mV. Intestinal absorption study depicted 18.3%, 21.5%, 41.5%, 98.7% absorption of DHA with SNEDDS-based formulation in comparison to 8.2%, 15.1%, 28.8%, 46.1% absorption of DHA with oil-based marketed formulation after 0.5, 1, 2 and 4 h. DHA concentration in brain homogenate was found to be increased to 2.6-fold in comparison to DHA-marketed formulation. This could be ascribed to enhanced dispersibility and bioavailability of DHA from nanosized formulation.Conclusion: The developed formulation led to enhanced dispersibility and bioavailability of DHA due to the formation of nanodroplets.

FORMULATION AND EVALUATION OF SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEM FOR SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT OF POORLY WATER SOLUBLE WITHAFERIN A

Withaferin A, a steroidal lactone which is present in dry root extract of Withania somnifera (WSE), is reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study is to enhance the dissolution rate and oral bioavailability of WSE by incorporating it in self nano emulsifying drug delivery system (SNEDDS). Capmul MCM-based SNEDDS formulation with Tween 20 as surfactant and ethanol as co surfactant was developed for oral delivery of withaferin A. Optimised SNEDDS was evaluated for its self-emulsification time and viscosity, droplet size. The optimised SNEDDS formulation containing withaferin A, Capmul MCM(12.4%), Tween 20 (58.2%) and ethanol (29%), and showed higher in vitro drug release as compared to pure WSE. These results demonstrate the potential use of SNEDDS for improving the oral bioavailability of poor water soluble compounds such as withaferin A.

Controlled release of glaucocalyxin – a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability

Objective: The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA).Material and methods: In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control.Results: In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged Tmax and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet.Conclusion: It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

Evaluation of Surfactant Effect on Self Micro Emulsifying Drug Delivery System (SMEDDS) of Lercanidipine Hydrochloride: Formulation and Evaluation

The aim of present research work was to develop self microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of lercanidipine hydrochloride and to evaluate the effect of surfactant on the microemulsion existing area in the pseudo ternary diagram. Based on the solubility studies, capmul MCM C8 as oil, brij 35 and cremophor EL as surfactants, and propylene glycol as a co-surfactant were selected. Pseudo ternary phase diagrams were developed with two surfactants individually and the concentration of each surfactant on oil solubilization, existence of the monophasic area in a phase diagram was evaluated. A wider microemulsion existing area with greater amount of oil solubilization (37.0 %) and lesser globule size (15.02 nm) was observed with cremophor EL compared to brij 35. Formulation composed of lercanidipine hydrochloride (3.23 %), capmul MCM C8 (16.13 %), cremophor EL (53.76 %), and propylene glycol (26.88 %) was optimized based on the self-emulsification time, globule size analysis, and in vitro dissolution studies. Optimized formulation was evaluated further for UV spectra, cloud point, viscosity, robustness to dilution, transmission electron microscopy, and ex vivo permeation studies. SMEDDS was found to be promising in improving solubility and permeability of lercanidipine hydrochloride that are proven by in vitro dissolution and permeation studies.

Development and Pharmacokinetic Evaluation of Industrially Viable Self-microemulsifying Drug Delivery Systems (SMEDDS) for Terbinafine

Objective: The aim of this study was to develop a formulation for lymphatic uptake with enhanced solubility of antifungal drug, terbinafine by use of self-microemulsifying drug delivery system (SMEDDS); suitable enough to be an industrially feasible and acceptable dosage form. Methods: Fabrication of pseudo ternary phase diagram was done with suitable oils, surfactants and co-surfactants. The optimized formulation was characterised for droplet size, polydispersity index, zeta potential, cross-polarized light microscopy, thermodynamic stability, viscosity, capsule compatibility and evaluated for in vitro- in vivo parameters. The formulation was tested in animal model for lymphatic uptake with and without chylomicron blocking agent followed by the pharmacokinetic evaluation of the same. Results: The self-emulsification time, droplet size, polydispersity index of the optimized formulation remained unaffected in different media (water, 0.1N HCl and phosphate buffer pH 6.8) over stability conditions and with time. Crossed-polarized light microscopy examination of diluted SMEDDS formulation indicated that the dispersion was an isotropically stable system. The rate of dissolution for SMEDDS formulation was almost double as compared to marketed formulation (Lamisil®). Current investigation indicated a potential for lymphatic uptake of lipid based SMEDDS formulation with enhanced solubility of the candidate drug terbinafine. The optimum formulation of terbinafine SMEDDS when orally administered to rat with and without chylomicron flow blocking agent (cycloheximide) showed the area under the curve (AUC0-48hrs) as 10168.17 ng h/ml and 7425.44 ng h/ml respectively indicating the absorption through the lymphatic route. Thus, the study shows use of SMEDDS formulation for the drug delivery by lymphatic uptake.