Solid Self-microemulsifying Drug Delivery Research Articles

Pharmacokinetic and toxicological assessment of a solid self-microemulsifying drug delivery system (S-SMEDDS) of kaempferia parviflora in rats

Kaempferia parviflora (KP), renowned as an alternative medicine, has gained widespread acclaim for its efficacy in male sexual enhancement and anti-inflammatory applications. However, methoxyflavones, its primary compound, poses challenges due to inherent low water solubility and limited oral absorption. This study aims to develop a novel solid self-microemulsifying drug delivery system for KP (KPS-SMEDDS) and to investigate the pharmacokinetic profile and acute toxicity. The liquid self-microemulsifying drug delivery system for KP (KPL-SMEDDS) was formed by combining Neobee® M − 5 (90 %) with a mixture of surfactant (10 %) consisting of Kolliphor® EL and polyethylene glycol 400 in a ratio of 1:2. Consequently, the KPL-SMEDDS was transformed into a powdered form by employing Sipernat® 22S as an absorbent in a 1:1 ratio. The developed formulations were subsequently evaluated for their physicochemical properties, in vitro dissolution tests, and in vivo oral absorption in rats by using methoxyflavones as the markers for quantitation. The findings demonstrated that the use of KPL-SMEDDS and KPS-SMEDDS improved the dissolution rate of methoxyflavones in 0.1 N HCl in comparison to KP powder. Comparative analysis revealed that the KPS-SMEDDS exhibited a significantly higher maximum drug concentration (Cmax) and area under the curve (AUC) values in comparison to the conventional KP extract. Notably, the KPS-SMEDDS formulation at an oral dose of 250 mg/kg remarkably increased the bioavailability of polymethoxyflavones up to 2.7- to 3-fold. Furthermore, acute oral toxicity assessment revealed no statistically significant alterations in clinical observations or biochemical parameters. These compelling findings underlined the potential of the KPS-SMEDDS formulation to augment the absorption and bioavailability of methoxyflavones, establishing its safety as an oral supplement.

A review of strategies for the development of solid self-microemulsifying drug delivery system

A review of strategies for the development of solid self-microemulsifying drug delivery system

Solid self-microemulsifying drug delivery system (S-SMEDDS) prepared by spray drying to improve the oral bioavailability of cinnamaldehyde (CA)

The aim of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) of cinnamaldehyde (CA) by spray drying technique to improve the oral bioavailability of CA. The preparation of CA S-SMEDDS with maltodextrin as the solid carrier, a core-wall material mass ratio of 1:1, a solid content of 20% (w/v), an inlet air temperature of 150 °C, an injection speed of 5.2 mL/min, and an atomization pressure of 0.1 MPa was determined by using the encapsulation rate as the index of investigation. Differential scanning calorimetry (DSC) revealed the possibility of CA being encapsulated in S-SMEDDS in an amorphous form. The in-vitro release showed that the total amount of CA released by S-SMEDDS was approximately 1.3 times higher than that of the CA suspension. Pharmacokinetic results showed that the relative oral bioavailability of CA S-SMEDDS was also increased to 1.6-fold compared to CA suspension. Additionally, we explored the mechanism of CA uptake and transport of lipid-soluble drugs CA by S-SMEDDS in a Caco-2/HT29 cell co-culture system for the first time. The results showed that CA S-SMEDDS uptake on the co-culture model was mainly an energy-dependent endocytosis mechanism, including lattice protein-mediated endocytosis and vesicle-mediated endocytosis. Transport experiments showed that CA S-SMEDDS significantly increased the permeability of CA in this model. These findings suggested that CA S-SMEDDS is an effective oral solid dosage form for increasing the oral bioavailability of lipid-soluble drug CA.

Rosuvastatin-loaded solid SMEDDS: an innovative approach for solubility augmentation and improved pharmacodynamic profile

The objectives undertaken in current work were to develop a new solid self-microemulsifying drug delivery system (S-SMEDDS) for poorly water-soluble Rosuvastatin Calcium (RST) and evaluate its antihyperlipidemic activity in rodent model. Solubility assessment in variety of excipients, screening studies and optimization of pseudoternary plots helped in development of liquid SMEDDS. Liquid SMEDDS of RST contained Capryol 90, Kolliphor EL and Transcutol HP as oil phase, surfactant and co-surfactant respectively which were evaluated for release, self-emulsification ability, percentage transmittance and globule size. Florite RE was used as the adsorbent to transform the optimized liquid SMEDDS into non-coherent powder which was then examined for micromeritic properties, solid state characterization and in vitro dissolution studies. It was additionally investigated for antihyperlipidemic activity in rats subjected to high fat diet. Optimized liquid SMEDDS of RST was found to undergo a swift transformation in a microemulsion having globule size in nanometric size range with consistent size distribution. The liquid SMEDDS adsorbed on Florite RE exhibited favorable micromeritic properties and spherical shape. XRD studies indicated amorphization of RST due to its molecular dispersion in S-SMEDDS. Enhanced in vitro rate of dissolution of optimized formulation was observed in comparison to pure drug and commercial product. There was considerable reduction (p < 0.001) in serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C), very low-density lipoproteins (VLDL-C) when S-SMEDDS was administered and increment in high-density lipoproteins (HDL-C) level compared to plain drug suspension. RST S-SMEDDS holds great potential for enhancement of its physiochemical along with biological attributes.

Cinnamon oil solid self-microemulsion mediates chronic mild stress-induced depression in mice by modulating monoamine neurotransmitters, corticosterone, inflammation cytokines, and intestinal flora

Cinnamon oil (CO) is a classic Chinese medicine with excellent soothing effects on exhaustion, weakness and depression. Cinnamaldehyde is the main active ingredient of cinnamic oil. Although CO have antidepression-like effects, limited information is available. Furthermore, the disadvantages of CO, such as low oral availability and difficult portability, limit its development. In this study, a Cinnamon Oil Solid Self-Microemulsifying Drug Delivery System (CO-S-SME) was designed, prepared. In addition, we explored the effects and mechanisms of CO-S-SME on chronic unpredictable mild stress (CUMS)-induced depression-like behavior, monoamine neurotransmitters, inflammatory factors, intestinal flora in mice. Mice were subjected CUMS to establish the depression model. The antidepressant effect of CO-S-SME was evaluated by behavioral tests. In addition, the expression levels of neurotransmitters, corticosterone (CORT) and inflammatory factors in CUMS mice were analyzed by enzyme-linked immunosorbent assay. In addition, we explored the effects of CO-S-SME on the diversity and richness of intestinal flora of mice in each group. Behavioral tests showed that CO-S-SME could effectively improve depression-like behaviors in CUMS mice. Specifically, CO-S-SME treatment effectively increased neurotransmitter levels and reduced the expressions of corticosterone and inflammatory factors in CUMS mice. CO-S-SME also changed the intestinal flora composition, decreased the ratio of Firmicutes to Bacteroidetes, reduced relative abundances of Lactobacillus, modulated Alpha diversity and beta diversity. These results suggest that CO-S-SME an act as a good antidepressant, exhibiting effects via monoamine neurotransmitters, CORT, inflammation cytokines, and intestinal flora.

Preparation and evaluation of ibrutinib lipid-based formulations

Ibrutinib is an anti-cancer drug, mainly used for treating B-cell malignancies. Because of its low water solubility and poor absorption in vivo, the bioavailability is extremely low, only 2.9%. In this study, a solid self-microemulsifying drug delivery system based on the lipid matrix was designed and prepared for ibrutinib. The composition of the self-microemulsion of ibrutinib includes oil phase Caprylic/Capric Triglyceride (Captex®335), surfactant Tween-80, and co-surfactant Diethylene glycol monoethyl ether (Transcutol HP). And the mesoporous silica SBA-15 was selected as an adsorbent to prepare solid powder preparations using the spray-drying method, which significantly improved its dispersibility and stability, and contributed to reducing the particle size and long-term preservation in gastric and intestinal fluids. The in vivo pharmacokinetic study of beagles showed that compared with commercial ibrutinib capsules, the relative oral bioavailability of ibrutinib capsules based on lipid matrix increased to 467.60%. In summary, the lipid-based solid preparation is a promising platform that can effectively improve the oral absorption of ibrutinib.

Quality-by-design strategy for the development of arteether loaded solid self-micro emulsifying drug delivery systems

The present work is conducted to develop the innovative micro sized solid oral dosage forms of Arteether using a Quality by Design technique to increase the solubility and bioavailability. The quantity of oil and the co-surfactant-surfactant ratio was employed as parameters in DoE for drug-loaded SMEDDS optimization. The particle size and zeta potential of these formulations were found to be 120 nm and −19.8 mV respectively. The studies show that 68 ± 0.2% of the drug is entrapped in SMEDDS. The solubility and in vitro dissolution performance of both drugs in self-nano emulsifying drug delivery system formulations was improved significantly as compared to pure drugs and marketed products and the in vivo studies confirmed it. A nearly 8.25-fold increase in permeability compared to AE in its pure form was observed with SMEDDS. In addition, to increase patient compliance, the liquisolid compaction technique was utilized to convert the best batch of liquid SMEDDS into solid SMEDDS, which were then encapsulated in enteric-coated capsule shells. In vivo studies in rabbits revealed that there was an increase in 8.5247% absolute bioavailability of self-nano emulsifying drug delivery system formulations compared to pure drugs with the area under the curve of Arteether from formulation was 691.2823 ± 024.13 in comparison to that of pure Arteether 79.8 ± 16.27. The Cmax was enhanced for artemether from 2.361879 ± 1.12 to 135.3684 ± 10.28. The developed formulation strategy would be potential alternative approach to enhance the bioavailability of Arteether.

Development and Optimization of Vitamin D3 Solid Self-Microemulsifying Drug Delivery System: Investigation of Flowability and Shelf Life.

We report herein the design of a solid self-microemulsifying drug delivery system (SMEDDS) of vitamin D3 for augmentation of its solubility and dissolution. The studies employed a 32 full factorial design by employing JMP 13.2.1, software for preparation of liquid SMEDDS. Further, the prediction profiler was utilized to optimized liquid SMEDDS-Vit.D3 (OF) formulation. The solidification of liquid SMEDDS-Vit.D3 formulation was carried out by physical adsorption over Neusilin US2 and Aerosil 200 carriers. Solid-state evaluation of SMEDDS-Vit.D3 suggested the transformation of crystalline to amorphous form of Vit.D3 which is responsible for imparting more aqueous solubility and thus enhancement in dissolution behaviour. The investigation of flow behaviours viz. flow function (FF) and effective angle of wall friction (EAWF) of solid SMEDDS-Vit.D3 was performed using powder flow tester. Solid SMEDDS-Vit.D3 prepared using Neusilin US2 showed good flow behaviour and hence was developed into tablets. The tablets showed good quality control parameters as per pharmacopeial standards. The in vitro dissolution studies demonstrated more dissolution of Vit.D3 in SMEDDS (liquid, solid, and tablet) when compared to the unprocessed drug. The shelf life (T90) of tablets was reported to be 28.12 months suggesting excellent stability of Vit.D3 in solid SMEDDS. In nutshell, our research works explore the utilization of SMEDDS for the oral delivery of Vit.D3 to gain maximum health-related benefits.

Design, Characterization, and Evaluation of Diosmetin-Loaded Solid Self-microemulsifying Drug Delivery System Prepared by Electrospray for Improved Bioavailability.

Diosmetin (DIOS) is a functional compound with poor water solubility, bad permeability, and crystal form. Self-microemulsifying drug delivery system (SMEDDS) was an effective formulation to overcome these shortcomings. In this study, liquid SMEDDS was prepared using Capmul® MCM C8 EP/NF, Cremophor EL, and PEG 400 (2:5.6:2.4, w/w/w) as excipients. Then, the novel technology of electrospray solidified liquid SMEDDS and prepared solid SMEDDS for inhibiting crystallization. Polyvinyl pyrrolidone (PVP) was used as carrier to construct DIOS-loaded solid SMEDDS, with polyethylene oxide (PEO) contributing to the formation of regular sphere in the process of spinning. The particle size of solid SMEDDS (194 ± 5nm) was much bigger than of liquid SMEDDS (25 ± 1nm), while DIOS-loaded solid SMEDDS showed greater dissolution rates in pH 1.2 and pH 6.8 media through in vitro drug release study. The solid nanoparticles were smooth and uniform from the graph of a scanning electron microscope (SEM). The graph of a transmission electron microscope (TEM) showed that small droplets were loaded in the matrix. Furthermore, DIOS was encapsulated by matrix in amorphous state via differential scanning calorimetry (DSC) and attenuated total reflection Fourier transform infrared (ATR-FTIR). The crystalline of DIOS was not formed in solid SMEDDS due to the characteristic peaks of DIOS disappeared in X-ray diffraction (XRD) pattern. Therefore, the oral bioavailability of DIOS improved significantly compared with liquid SMEDDS (4.27-fold). Hence, solid SMEDDS could improve the solubility and bioavailability of DIOS, through transfer of the state of crystalline to amorphous by electrospray technology.

DoE-Based Solid Self-microemulsifying Drug Delivery System (S-SMEDDS) Approach for Improving the Dissolution Properties of Raltegravir Potassium

DoE-Based Solid Self-microemulsifying Drug Delivery System (S-SMEDDS) Approach for Improving the Dissolution Properties of Raltegravir Potassium

Natural bio functional lipids containing solid self-microemulsifying drug delivery system of Canagliflozin for synergistic prevention of type 2 diabetes mellitus

Type 2 Diabetes Mellitus (T2DM) is one of the prevalent metabolic disorders and is the leading cause of death across the globe. In the present invention, we reported significant synergistic anti-diabetic efficacy of novel SGLT II inhibitor, Canagliflozin (CFZ) with natural phytoconstituent, Trigonelline (TGL) in fenugreek oil using a self-microemulsifying based formulation. The optimized liquid SMEDD formulation (NADF) containing fenugreek oil (18.11% w/w), vitamin E TPGS (53.40% w/w) and linalool (10.12% w/w) were optimized by Design of Experiments and produces nanoparticulate stable microemulsion in vitro. Conversion to solid SMEDDS (NADF-SD) was facilitated by adsorption onto natural biosorbent coffee husk. The optimized solid formulation containing CFZ was in amorphous state with enhanced surface area, negligible chemical incompatibility and uniform drug content. Scanning electron microscopy validated the powdered SMEDDS′ spherical form. The release behavior of CFZ in NADF-SD in diverse biorelevant environments is enhanced by in vitro dissolution. Furthermore, neither pure CFZ nor the marketed product had any food impact. The permeability of the jejunum intestinal segment in rats was remarkable, as validated by confocal microscopy. In comparison to a pure drug and a commercial product, these trials show a 3.99 and 2.56 fold increase in Cmax and a 2.23 and 1.56 fold increase in AUC0-24h, respectively. Through biochemical levels, urine glucose excretion investigations, and SGLT II expression in rats, pharmacodynamic examination of improved NADF-SD demonstrates enhanced anti-diabetic effectiveness of CFZ. In a nutshell, this natural lipid-based micro particulate system is well-suited for this drug's anti-diabetic activity and synergy with CFZ.

Extraction of Tanshinones Rich Extract of Danshen (Salvia Miltiorrhiza Bunge) Root Using Adsorptive (Non-Ionic) Macroporous Resins

Tanshinones are an important lipophilic, bioactive diterpenoid group of danshen roots with many pharmacological activities. In this study, tanshinones rich extract of danshen roots, a typically valuable product of danshen, was prepared through a two-step process of extraction and purification. In which, adsorptive (non-ionic) macroporous resins were exploited in the purification step to remove impurities and enrich tanshinones. The obtained refined extract was red brownish dry powder with the following characteristics: loss on drying of 4.04 ± 0.18%, tanshinone IIA and cryptotanshinone content of 10.55 ± 0.21% and 5.78 ± 0.64%, respectively (the results met the requirements of the Tanshinones monograph in The Chinese Pharmacopoeia 2015). The overall yield of the established extraction process was 2.21 ± 0.12%, calculated by the weight of dry extract.&#x0D; Keywords: Tanshinones, danshen, macroporous resins, tanshinone IIA, cryptotanshinone.&#x0D; References&#x0D; [1] X. Yan, Overview of Modern Research on Danshen, G. Du, J. Zhang, Danshen (Salvia Miltiorrhiza) in Medicine, Springer, Germany, Vol. 2, 2014, pp. 3-17.[2] C. Y. Su, Q. L. Ming, K. Rahman, H. Ting, L. P. Qin, Salvia miltiorrhiza: Traditional Medicinal Uses, Chemistry, and Pharmacology, Chinese Journal of Natural Medicines, Vol. 13, No. 3, 2015, pp. 163-182, https://doi.org/10.1016/S1875-5364(15)30002-9.[3] Y. Cui, B. Bhandary, A. Marahatta, G. H. Lee, B. Li, D. S. Kim, S. W. Chae, H. R. Kim, H. J. Chae, Characterization of Salvia Miltiorrhiza Ethanol Extract as An Anti-osteoporotic Agent, BMC complementary and alternative medicine, Vol. 11, No. 1, 2011, pp. 120-131, https://doi.org/10.1186/1472-6882-11-120.[4] J. Li, H. A. Chase, Development of Adsorptive (Non-ionic) Macroporous Resins and Their Uses in The Purification of Pharmacologically-Active Natural Products From Plant Sources, Natural product reports, Vol. 27, No. 10, 2010, pp. 1493-1510, https://doi.org/10.1039/c0np00015a.[5] Tanshinones, The Chinese Pharmacopoeia, China, 2015, pp. 398-399.[6] G. Tian, T. Zhang, Y. Zhang, Y. Ito, Separation of Tanshinones From Salvia miltiorrhiza Bunge by Multidimensional Counter-Current Chromatography, Journal of Chromatography A, Vol. 945, No. 1-2, 2002, pp. 281-285, https://doi.org/10.1016/S0021-9673(01)01495-9.[7] D. Wu, X. Jiang, S. Wu, Direct Purification of Tanshinones From Salvia miltiorrhiza Bunge by High‐speed Counter‐current Chromatography Without Presaturation of The Two‐phase Solvent Mixture, Journal of Separation Science, Vol. 33, No. 1, 2010, pp. 67-73, https://doi.org/10.1002/jssc.200900491.[8] M. Liu, X. H. Xia, Study on The Chemical Stability of Tanshinone IIA, Zhong Yao Cai, Vol. 33, No. 4, 2010, pp. 606-609, PMID: 20845791 (In Chinese).[9] X. Bi, X. Liu, L. Di, Q. Zu, Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza, Molecules, Vol. 21, No. 456, 2016, pp. 1-15. https://doi.org/10.3390/molecules21040456.&#x0D; &#x0D;

Preparation and evaluation of solid self-microemulsifying drug delivery system of eprosartan mesylate using vegetable oils

The current work deals with the designing of a solid self-microemulsifying drug delivery system (S-SMEDDS) of eprosartan mesylate (EPM) for improved bioavailability by enhancing the intestinal permeability of EPM. Two L-SMEDDSs containing EPM (OF9 and PF5) were formulated successfully using Tween 80 as surfactant, PEG 400 as cosurfactant and two different oil phases (i.e., 10% oleic acid and 50% peppermint oil), separately. The L-SMEDDSs were characterized by TEM image analysis and evaluated for self-emulsification efficiency, thermodynamic stability, droplet size and zeta potential, transmittance, cloud point, rheology and drug content. S-SMEDDSs containing EPM were prepared using OF9 and PF5 L-SMEDDSs, when these were separately adsorbed on to the surface of Aerosil 200, which displayed excellent flow properties, high drug content, and nanometer ranged particle size. These prepared S-SMEDDSs (OF9S4 and PF5S4) were characterized by SEM, FTIR, DSC and XRD analyses. Prepared OF9S4 S-SMEDDS exhibited significantly enhanced (p < 0.05) in vitro drug release and enhanced ex vivo drug permeability than the pure EPM and L-SMEDDSs (OF9 and PF5). In addition, S-SMEDDSs remained stable enough at 40 ± 2 °C/75 ± 5% RH after 6 months of storage. Thus, it can be concluded that prepared S-SMEDDSs (OF9S4 and PF5S4) can facilitate the effective delivery of poorly soluble drugs with better therapeutic advantage.

Formulation optimization of solid self-microemulsifying pellets for enhanced oral bioavailability of curcumin

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0–τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.

PH-Independent Dissolution and Enhanced Oral Bioavailability of Aripiprazole-Loaded Solid Self-microemulsifying Drug Delivery System.

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12h) as compared with commercial tablet (3.33 ± 0.94h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life

Aim The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. Methods A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. Results The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = –25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. Conclusions The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

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).&#x0D; 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.&#x0D; 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%.&#x0D; 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.

Self-microemulsion Technology for Water-insoluble Drug Delivery

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate.

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability.Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder.Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions.Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.