Microemulsifying Drug Delivery System Research Articles

Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin.

In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC50) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.

Formulation Development and Evaluation of Solid Self Microemulsifying Drug Delivery System of Azelnidipine

This study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for poorly soluble azelnidipine using Capryol 90 as the oil, Tween 80 as the surfactant, and transcutol-HP as the co-surfactant. A factorial design was used to optimize the formulation, and Neusilin UFL2 was used as an adsorbent to convert the liquid SMEDDS to solid SMEDDS. The optimized formulation had a particle size of 80.5nm, a transmittance of 98.2%, a zeta potential of -3.1 mV, and a polydispersibility index of 0.226. The solid SMEDDS tablet exhibited improved drug release (99.4% in 60 minutes) compared to the marketed tablet (67.09.75%) and pure drug (26.17%). This study demonstrates the potential of the SMEDDS approach to enhance the solubility and in-vitro drug release of poorly soluble drugs such as azelnidipine.

Dolutegravir Loaded Solid Self-Micro-Emulsifying Drug Delivery System for Enhanced Solubility and Dissolution

Dolutegravir sodium (DG) is a recently approved antiretroviral drug belonging to BCS class II having poor aqueous solubility and only 16% oral bioavailability. Hence aim of the present work was to develop solid self micro-emulsifying drug delivery system (S-SMEDDS) of Dolutegravir for enhanced solubility and dissolution behaviour. Initially, solubility of DG was checked to select oil, surfactant, and co-surfactant. Pseudo ternary phase diagram was constructed to identify microemulsion region. Liquid SMEDDS of DG were prepared using Campul MCM, Tween 80 and Transcutol P as oil, surfactant, and co-surfactant, respectively. The effect of different oil, surfactant and co-surfactant concentrations on particle size, zeta potential and %transmittance was studied using Box–Behnken factorial design. The obtained liquid SMEDDS was evaluated for its thermodynamic stability, globule size, robustness to dilution, viscosity, dye solubilization test, cloud point, etc. Satisfactory formulations of liquid SMEDDS were converted to solid form by adsorption technique using Neusilin US2 as a solid carrier. Evaluation of S-SMEDDS showed that solubility of DG in S-SMEDDS increases from 0.270 to 33.52 mg/mL. In-vitro drug release of S-DG4 showed 99.86 ± 1.47% drug release within 120 minutes while plain DG showed 32.55 ± 1.52%. Hence study revealed that S-SMEDDS is a promising approach to enhance solubility, dissolution and hence bioavailability of poorly aqueous soluble drug like DG.

Enhanced Antioxidant and Anti-Inflammatory Effects of Self-Nano and Microemulsifying Drug Delivery Systems Containing Curcumin.

Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due to an active ingredient isolated from the plant, called curcumin. However, the extremely poor water-solubility of curcumin often limits the bioavailability of the drug. The aim of our experimental work was to improve the solubility and thus bioavailability of curcumin by developing self-nano/microemulsifying drug delivery systems (SN/MEDDS). Labrasol and Cremophor RH 40 as nonionic surfactants, Transcutol P as co-surfactant and isopropyl myristate as the oily phase were used during the formulation. The average droplet size of SN/MEDDS containing curcumin was between 32 and 405 nm. It was found that the higher oil content resulted in larger particle size. The drug loading efficiency was between 93.11% and 99.12% and all formulations were thermodynamically stable. The curcumin release was studied at pH 6.8, and the release efficiency ranged between 57.3% and 80.9% after 180 min. The results of the MTT cytotoxicity assay on human keratinocyte cells (HaCaT) and colorectal adenocarcinoma cells (Caco-2) showed that the curcumin-containing preparations were non-cytotoxic at 5 w/v%. According to the results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays, SNEDDS showed significantly higher antioxidant activity. The anti-inflammatory effect of the SN/MEDDS was screened by enzyme-linked immunosorbent assay (ELISA). SNEDDS formulated with Labrasol as surfactant, reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels below 60% at a concentration of 10 w/w%. Our results verified the promising use of SN/MEDDS for the delivery of curcumin. This study demonstrates that the SN/MEDDS could be promising alternatives for the formulation of poorly soluble lipophilic compounds with low bioavailability.

Solid self‑emulsifying pellets: Solubility enhancement for oral delivery of poorly soluble BCS Class II drug

The review focused on technique of solid self-emulsifying pellets (SEPs) for solubility enhancement of poorly water soluble drug. The oral route of administration has been and still is currently the primary route of drug delivery owing to its potential advantages compared to the other routes. The solubility enhancement process of hydrophobic drugs plays a key role in the formulation development to achieve the bioavailability and therapeutic action of the drug at the target site.1 Around 40% of probe new drugs are characterized as belonging to class II in the BCS classification (poorly water soluble and highly permeable), giving rise to poor and erratic oral bioavailability. The solid SEPs system combines the advantages of liquid Self emulsifying drug delivery system with those of solid dosage form, which can overcome the limitations of liquid formulations and improve the storage stability and patient compliance. To enhance the dissolution and oral absorption of water insoluble drug selfmicroemulsifying pellets develop and evaluated. SEPs pellets showed a significant quicker redispersion rate than the dissolution rate of commercial tablets. The solid SEPs pellets might be an encouraging strategy to improve the oral absorption of Poorly water soluble drug and the extrusion–spheronization method is a feasible technology for the solidification of liquid SMEPs. Self microemulsifying drug delivery system (SEPs) as an effective bioavailability enhancement pharmaceutical technology has been widely used during the recent years and have some successful products in the market (e.g. Neoral®, Norvir® and Fortovase®).
 Keywords: Self Emulsifying Pellets, Bioavailability, Solubility, extrusion–spheronization, Biopharmaceutical Classification.

Optimized self-microemulsifying drug delivery system improves the oral bioavailability and brain delivery of coenzyme Q10

Our study aimed to develop a self-microemulsifying drug delivery system for the poorly aqueous-soluble drug Coenzyme Q10, to improve the dissolution and the oral bioavailability. Excipients were selected based on their Coenzyme Q10 solubility, and their concentrations were set for the optimization of the microemulsion by using a D-optimal mixture design to achieve a minimum droplet size and a maximum solubility of Coenzyme Q10 within 15 min. The optimized formulation was composed of an oil (omega-3; 38.55%), a co-surfactant (Lauroglycol® 90; 31.42%), and a surfactant (Gelucire® 44/14; 30%) and exhibited a mean droplet size of 237.6 ± 5.8 nm and a drug solubilization (at 15 min) of 16 ± 2.48%. The drug dissolution of the optimized formulation conducted over 8 h in phosphate buffer medium (pH 6.8) was significantly higher when compared to that of the Coenzyme Q10 suspension. A pharmacokinetic study in rats revealed a 4.5-fold and a 4.1-fold increase in the area under curve and the peak plasma concentration values generated by the optimized formulation respectively, as compared to the Coenzyme Q10 suspension. A Coenzyme Q10 brain distribution study revealed a higher Coenzyme Q10 distribution in the brains of rats treated with the optimized formulation than the Coenzyme Q10 suspension. Coenzyme Q10-loaded self microemulsifying drug delivery system was successfully formulated and optimized by a response surface methodology based on a D-optimal mixture design and could be used as a delivery vehicle for the enhancement of the oral bioavailability and brain distribution of poorly soluble drugs such as Coenzyme Q10.

In vitro and in vivo evaluation of cinnamaldehyde Microemulsion-Mucus interaction.

The current investigation explores the possible mechanism of the microemulsion drug delivery system to improve the oral bioavailability of cinnamaldehyde (CA), an important food spice, from the perspective of the microemulsion-mucus system. The cinnamaldehyde microemulsion (CA-ME) was prepared by the water titration method combined with the pseudo-ternary phase diagram. The dynamic analysis was applied to detect the drug release in vitro. An intestinal mucosal injury test was conducted to evaluate the safety of CA-ME and drug absorption across the intestinal tract of rats was investigated through an Ussing chamber system. The rheology of blank mucus and drug-loaded mucus was investigated using a rheometer. The bioavailability of CA-ME in rats was evaluated through pharmacokinetic characteristics. The ratio of optimal prescription was Tween 80: 1,2-propanediol: vitamin E oil: CA: water=24.3:4.8:5:7.5:58.4. The droplets were uniform in size and evenly dispersed. Rheological studies showed that the microemulsion-mucus system all exhibit pseudoplastic fluid behavior, and CA-ME increased the viscosity of the mucus to a certain extent. Compared with CA solution, CA-ME promoted the absorption of CA in various intestinal segments, especially the ileum. Pharmacokinetic experiments showed that the relative bioavailability of CA-ME was enhanced 2.5-fold higher than that of CA solution. ME as a carrier for lipophobic substances, may increase the viscosity of the intestine mucus system to obtain longer residue time and better absorption. PRACTICAL APPLICATIONS: In this study, in vitro absorption Ussing model was combined with rheological and pharmacokinetic analysis to systematically analyze the intestinal mucus mechanism of microemulsion to improve the oral bioavailability of cinnamic aldehyde. It laid the foundation for exploring the absorption and transport of drugs in the intestinal mucus barrier.

Design and Development of Solid SMEDDS and Liquisolid Formulations of Lovastatin, for Improved Drug Dissolution and In vivo Effects-a Pharmacokinetic and Pharmacodynamic Assessment.

Lovastatin (Lov) is a lipid-lowering agent, with 5% bioavailability (BA) due to extensive first pass metabolism and poor solubility. To enhance dissolution and in vivo effects, Lov solid self microemulsifying drug delivery system (SMEDDS) and liquisolid systems were developed and evaluated to select superior one. Solubilities were determined in oils, surfactants, and cosurfactants. Ternary phase diagrams were constructed and selected the one which showed maximum emulsion zone. In vitro dissolution, DSC, SEM and PXRD studies were used to characterize the developed formulations. In vivo studies were conducted on optimal formulations in wistar rats. Based on solubilities, Capmul PG8 and Capmul MCM were preferred as oils, Labrasol and Transcutol P as surfactant and cosurfactant. Here, Syloid XDP carrier showed better adsorption capacity among others, hence was used in optimal solid SMEDDS (SX) and liquisolid (LS) formulations. Dissolution study results showed significant improvement in release when compared to pure drug. DSC, SEM, and PXRD results indicated the loss of drug crystallinity in optimal formulations. In pharmacokinetic (PK) study, SX and LS showed 2.57 and 1.43 fold improvements in AUC, when compared to that of coarse suspension (CS). In pharmacodynamic (PD) study, hyperlipidemia was induced by Triton X-100. CS and LS treatments showed a decline in hyperlipidemic levels at 4h. But, SX-treated group showed early onset of decline at 2h. Further, the duration of anti-hyperlipidemia was at least 12h extra when compared to CS and LS. This study confirmed the superiority of SX over LS in PK and PD effects.

Transdermal Delivery of Indirubin-Loaded Microemulsion Gel: Preparation, Characterization and Anti-Psoriatic Activity.

Psoriasis is an immune disease caused by rapid and incomplete differentiation of skin basal cells. Natural products such as indirubin have historically served as excellent sources for the treatments of psoriasis. However, the poor solubility and bioavailability due to its plane and rigid crystal structure, which limits its efficacy. Herein, to improve the efficacy of indirubin, a hydrogel-based microemulsion drug delivery system was developed for transdermal delivery. The mean droplet size of the optimized microemulsion was 84.37 nm, with a polydispersity index (PDI) less than 0.2 and zeta potential value of 0~−20 mV. The transdermal flux and skin retention of indirubin at 24 h were 47.34 ± 3.59 μg/cm2 and 8.77 ± 1.26 μg/cm2, respectively. The optimized microemulsion was dispersed in carbomer 934 hydrogel to increase the consistency. The indirubin-loaded microemulsion gel was tested on an imiquimod-induced psoriasis mouse model. Results showed that this preparation can improve psoriasis symptoms by down-regulating the expression of IL-17A, Ki67, and CD4+T. This experiment provides great scalability for researchers to treat psoriasis, avoid first-pass effects, and increase the concentration of targeted drugs.

SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM OF URSOLIC ACID: FORMULATION DEVELOPMENT, CHARACTERIZATION, PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES FOR DIABETIC COMPLICATIONS

Objective: The objective of this study was to develop, characterize, and conduct pharmacokinetic and pharmacodynamic studies on ursolic acid solid self microemulsifying drug delivery system (UA-S-SMEDDS) for the treatment of diabetic complications. Methods: Liquid self microemulsifying drug delivery system (L-SMEDDS) were made with Capryol 90 as an oil, Cremophor EL as a surfactant, and polyethylene glycol (PEG) 400 as a co-surfactant. The surfactant and co-surfactant (Smix) ratios were calculated using a pseudo ternary phase diagram. At different pH levels and with water, the globule size, polydispersity index (PDI), zeta potential (ZP), and dilution were all assessed. S-SMEDDS has developed adsorption to a solid carrier by utilizing L-SMEEDS formulation. The powder properties, liquid retention potential, globule size, PDI, ZP, assay, and pharmacokinetic studies were all evaluated. The pharmacodynamic investigations of the S-SMEDDS formulation in streptozotocin (STZ) induced Wistar rats were evaluated using malondialdehyde (MDA) and glutathione (GSH) determination in tissues and section studies. Results: S-SMEDDS formulation was successfully developed with a droplet size of 163.4±1.475 nm, PDI of 0.251±0.042, a ZP of-21.3±1.02, an assay of 96.21±0.75%. The release studies showed 26.28% (0.1N HCl) and 83.57% (6.8 phosphate buffer) were released in 15 min. When comparing the pharmacokinetics of a UA-loaded S-SMEDDS to the coarse suspension, the S-SMEDDS (F2A) showed a 4.12 fold improvement in UA oral bioavailability. The pharmacodynamic results showed that S-SMEDDS was a higher recovery rate. Conclusion: The developed solid SMEDDS (F2A) formulation proved effective in treating diabetic complications in STZ induced Wistar rats by inhibiting the aldose reductase enzyme.

Formulation and Evaluation of Self Micro-Emulsifying drug delivery System of Carvedilol

The current work involves preparation and evaluation of self-micro emulsifying drug delivery system of carvedilol, an nonselective betablocker and alpha-1 blocker. Oral self micro-emulsifying drug delivery system of Carvedilol were prepared by studying the solubility in different oils, surfactants and co-surfactants and formulations were prepared using mixtures of oils, surfactants, and cosurfactants in various proportions. Based on the solubility study, the optimised self micro-emulsifying drug delivery system of carvedilol was prepared using Capryol 90 as oil phase and tween 20 and transcutol P as surfactant and co-surfactant, respectively. The formulations were evaluated for stability, globule size and in vitro performance. To estimate the drug content from various excipients, final microemulsion formulations and in vitro performance study, a stability-indicating validated high-performance liquid chromatography method was developed using Inertsil ODS-3V (150 mm×4.6 mm, 5 μm) high-performance liquid chromatography column. The method was validated for various parametes like accuracy, linearity, precision (intraday and interday) and robustness. All the validation parameters were in acceptable range. The developed method was found to be specific accurate and robust for estimation of carvedilol from its microemulsion formulations.

Preparation and Evaluation of a Novel Oral Microemulsion Drug Delivery System for Enhancing the Bioavailability of Diltiazem

Diltiazem, a calcium ion cellular influx inhibitor is known for its limited and variable bioavailability. This study is intended to explore the benefits of microemulsion formulation as an oral drug delivery system for immediate release to improve the bioavailability and efficacy of Diltiazem. Methods: Oil in water microemulsion was prepared using the simple water titration method. The optimized formulation was evaluated for physicochemical parameters like viscosity, pH, conductivity, and accelerated stability studies. In vitro release, diltiazem microemulsion was investigated.

Lipid-based emulsion drug delivery systems - a comprehensive review.

Lipid-based emulsion system - a subcategory of emulsion technology, has emerged as an enticing option to improve the solubility of the steadily rising water-insoluble candidates. Along with enhancing solubility, additional advantages such as improvement in permeability, protection against pre-systemic metabolism, ease of manufacturing, and easy to scale-up have made lipid-based emulsion technology very popular among academicians and manufacturers. The present article provides a comprehensive review regarding various critical properties of lipid-based emulsion systems, such as microemulsion, nanoemulsion, SMEDDS (self microemulsifying drug delivery system), and SNEDDS (self nanoemulsifying drug delivery system). The present article also explains in detail the similarities and differences between them, the stabilization mechanism, methods of preparation, excipients used to prepare them, and evaluation techniques. Subtle differences between nearly related terminologies such as microemulsion and nanoemulsion, SMEDDS, and SNEDDS are also explained in detail to clarify the basic differences. The present article also gives in-depth information regarding the chemical structure of various lipidic excipients, various possible chemical modifications to modify their inherent properties, and their regulatory status for rational selection.

Potensi Formulasi Self Microemulsifying Drug Delivery System (SMEDDS) Ekstrak Biji Kedelai (Glycine soja) Terhadap Penurunan Kolesterol pada Penyakit Jantung Koroner

Background: Coronary heart diseases (CHD) is a disorder that caused by blockage of coronary arteries due to the process of atherosclerosis which disrupts the blood supply to the heart muscle. According to Sample Registration System (SRS) Indonesia in 2014, CHD is a second highest cause of death after stroke that is 12,9% of all cause of death in Indonesia. Therefore, this study aims to examining the effect of soybean extract encapsulated with Self Microemulsifying Drug Delivery System (SMEDDS) on LDL levels in coronary heart model rats. Based on various study, isoflavone aglycone genistein is the main flavonoid in soybean seed that has potential as an antioxidant. To increase bioavailability of aglycone isoflavones, a SMEDDS is needed. In this regard, the purpose of this reseach is to examine the potential of soybean seed (Glycine soja) extract to reduced cholesterol in CHD.Methods: The method used is a literature review with literature sources in the form of relevant articles from the search engines, namely Google Scholar, Pubmed, ScienceDirect, and Research Gate. Inclusion criteria included journals containing the keywords “soybean (Glycine soja)”, “Coronary Heart Disease”, “SMEDDS”, and “genistein isoflavone aglycone”.Result: Isoflavone aglycone as an potential antioxidant that is able to bind free radicals and and also lowering LDL, Triglycerides, and glucose levels in hyperglycemic states and increasing HDL.Conclusion : Soybean seed extract with SMEDDS encapsulation have a potential to decrease LDL level in coronary heart disease.

FORMULATION AND EVALUATION OF SOLID SELF MICRO EMULSIFYING DISPERSIBLE TABLET OF PIROXICAM

Objective: The aim of this study was to formulate the solid self-micro emulsifying dispersible tablets for promoting the dissolution of Piroxicam.
 Methods: Solubility study test was performed to know the solubility of various oil phase, surfactants, cosurfactants. Self-emulsifying grading test was done by visual grading system. Ternary phase diagrams and droplet size analysis test were performed to screen and optimize the Piroxicam-self microemulsifying drug delivery system (SMEDS). Then microcrystalline cellulose (KG802) was added as a suitable adsorbent and dispersible tablet were prepared by wet granulation compression method.
 Results: The final composition of Piroxicam-SMEDS was oil phase (oleic acid, 23%), surfactant (Cremophor R H-40,61%), co-surfactant (PEG-400,16%) based on the result of solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams. Microcrystalline cellulose (KG802) was selected based on dissolution study (98.35%) and added to liquid Piroxicam-Smeds formulation to form dispersible tablets. The in vitro dissolution study showed 98.02 % of drug release from Piroxicam-SMEDS tablets.
 Conclusion: Piroxicam–Self microemulsifying dispersible tablets have increased the solubility and bioavailability of the Piroxicam to a greater extent. SMEDS formulation can help the solubility of poorly water-soluble drugs.

Conceptual design and optimization of self microemulsifying drug delivery systems for dapsone by using Box-Behnken design

Conceptual design and optimization of self microemulsifying drug delivery systems for dapsone by using Box-Behnken design

MSc. Development of the In-house Specifications and Study of the Stability of Self-nanoemulsifying Drug Delivery System Containing Rosuvastatin

This study develops the in-house specifications of self-nanoemulsifying drug delivery system (SNEDDS) containing rosuvastatin based on the following criteria: description, identification, droplet size (≤200 nm) and polydiversity index (not more than 0.3), drug proportion in the oil phase (≥ 90.0%), assay (≥ 95.0% and ≤105.0% of the labeled amount of rosuvastatin (C22H28FN3O6S). The criteria were validated and the results were suitable for identification and determination of rosuvastatin in SNEDDS. Additionally, the results of the stability study show that the rosuvastatin SNEDDS met the criteria of description, droplet size, PDI, assay and drug rate in the oil phase for 12-month storage under the long-term condition (12 months) and 6 months on accelerated condition.
 Keywords
 Rosuvastatin, SNEDDS, specification, droplet size, entrapment efficiency.
 References
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Polymeric Precipitation Inhibitor Assisted Supersaturable SMEDDS of Efavirenz Based on Experimental Observations and Molecular Mechanics.

Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz. The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance. Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach. The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product. The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.

Development, characterization, comparative pharmacokinetic and pharmacodynamic studies of iloperidone solid SMEDDS and liquisolid compact

Iloperidone (ILO) is an anti-psychotic, used in schizophrenia. It has low bioavailability (36%) due to low solubility and first pass effect. Oral solid self microemulsifying drug delivery system (SMEDDS) and liquisolid compact (LSC) of ILO were developed. The hypothesis is to test in vivo performance (PK and PD effects) of these delivery systems, as both systems improve dissolution. Based on solubility Capmul MCM, Labrafac WL 1349 were selected as oils, Lauroglycol 90 and PEG 600 were selected as surfactant and cosurfactant. Syloid XDP was optimized for adsorption of liquid SMEDDS. Syloid XDP and Aerosil 200 were optimized as carrier and coating material in the ratio of 15:1 w/w for liquisolid formulation. SEM and PXRD studies indicated no specific crystallinity due to bulkiness in both formulations, which showed similar flow and release behavior. Pharmacokinetic studies were performed for ILO Coarse suspension (CS), Tablet suspension (TS), optimized solid SMEDDS (A1X) and liquisolid compact (S3) in wistar rats. About 3.80 and 2.19-fold improvements in relative bioavailabilty were found for A1X and S3, respectively, when compared to CS. In comparison to TS, 2.61 and 1.51 fold improvements in bioavailability were found for A1X and S3, respectively. Further, Pharmacodynamic activity was studied by reversal of MK-801 induced hyperlocomotion in rats. A1X and S3 formulations showed maximum reversal after 15 min when compared to CS and found to have similar performance. Thus, in comparison to S3, A1X showed significant difference in pharmacokinetic effects but similar pharmacodynamic effects.