Oral solid gentamicin preparation using emulsifier and adsorbent

Self-emulsifying peptide drug delivery systems: How to make them highly mucus permeating

Tacrolimus is an immunosuppressant agent for the prevention and treatment of graft rejection in solid organ transplantation patients. Tacrolimus is a poorly water-soluble drug. Its absorption is further limited due to the involvement of an efflux transporter P-glycoprotein and metabolism via cytochrome P450. The objective of presentinvestigation was to develop and characterize a liquid self-microemulsifying drug delivery system (SMEDDS) and a solid SMEDDS by using bioenhancer excipients like Tween 20 and Tween 80, which are known for their inhibiting action on CYP 450 and P-glycoprotein efflux pump. Solubility of Tacrolimus was determined in various vehicles, including oils, surfactants and cosolvents. Pseudoternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized formulations were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and globule size analysis. The optimized liquid SMEDDS formulation contained 20% Phosal 53 MCT as oil, 60% Tween 20 as surfactant and 20% ethanol as cosolvent. Liquid SMEDDS was converted to solid SMEDDS by using Aerosil-200 and Florite-RE as inert solid adsorbents. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found to be 140.9 nm and 304.6 nm, respectively. DSC and XRD results of solid SMEDDS confirmed that the drug present in the formulation was in an amorphous state. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.76 and 2.27 years, respectively. The prepared liquid SMEDDS and solid SMEDDS containing bioenhancer excipients increase the in vitro dissolution rate of lipophilic Tacrolimus.

The present paper reports in situ lipidization as a novel approach for the design of Dox-self microemulsifying drug delivery system (SMEDDS). Dox-aerosol OT (AOT) ion pair complex (lipidized Dox), exhibited high log P value of 1.74, indicating lipophilic nature. The lipidized Dox revealed good solubility but limited stability in various oils. Rapid complex formation of Dox with AOT dissolved in oils, and the high partitioning of lipidized Dox (-90%) into the oily phase presented in situ lipidization as a strategy to overcome the limited chemical stability of lipidized Dox. SMEDDS was prepared by mixing the lipidizing agent AOT, the surfactant α-Tocopheryl-Polyethyleneglycol-1 000-Succinate (TPGS) and Capmul as the oil. Dox was suspended in the SMEDDS to obtain Dox-SMEDDS. Dox-SMEDDS on aqueous dilution, resulted in a microemulsion with globule size 196 ± 16.56 nm, and revealed slow release of Dox. Oral bioavailability study in rats revealed a 420% enhancement from Dox-SMEDDS compared to Dox solution. Dox-SMEDDS and control group revealed comparable superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in heart and kidneys suggesting safety of the Dox-SMEDDS. Efficacy study (tumor size reduction) in fibrosarcoma mouse model suggested Dox-SMEDDS as a promising oral delivery system for the treatment of cancer. In situ lipidization of Dox in SMEDDS presents a novel approach for the design of an orally bioavailable and promising formulation of Dox for oral administration.

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.

In the present study, we prepared an inclusion complex of methotrexate (MTX) with β-cyclodextrin (β-CD) in order to decrease its photosensitivity and enhance its aqueous solubility. Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability. The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/β-CD was found to be of 1:7, and the water-solubility of MTX was increased in an average of 10-fold. The photostability studies showed that the MTX became stable on exposure to light. Construction of pseudoternary diagrams were investigated to prepare a MTX/β-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential. The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39.42 nm. In vitro drug release in different pH media showed that the release profile of MTX from the MTX/β-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile. Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/β-CD loaded SMEDDS form of 1.57-fold. We concluded that the β-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route.

Evaluation of the stability and absorption of tacrolimus self-microemulsifying drug delivery system

Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT1) receptor that is indicated for the treatment of essential hypertension. It belongs to a class II drug in BCS classification i.e. low solubility and high permeability. One of the major problems with this drug is its low solubility in biological fluids which results into poor bioavailability after oral administration. The objective of present work was to develop a self microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of poorly water soluble Telmisartan. SMEDDS is a mixture of oil, surfactant, and cosurfactant, which are emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Psuedoternary phase diagrams were constructed to identify the efficient self-emulsifying region. A SMEDDS were further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, globule size, zeta potential, pH, refractive index, X-ray diffraction, Differential scanning calorimetry and in vitro dissolution studies. Optimized formulation was also compared with marketed product (Telma 20) in male spraguedawley rats. The pharmacokinetic study exhibited 1.54 fold increase in the oral bioavailability of Telmisartan SMEDDS compared with the Marketed product.

Highly mucus permeating and zeta potential changing self-emulsifying drug delivery systems: A potent gene delivery model for causal treatment of cystic fibrosis

Efforts in discovering new and effective neurotherapeutics are made daily, although most fail to reach clinical trials. The main reason is their poor bioavailability, related to poor aqueous solubility, limited permeability through biological membranes, and the hepatic first-pass metabolism. Nevertheless, crossing the blood–brain barrier is the major drawback associated with brain drug delivery. To overcome it, intranasal administration has become more attractive, in some cases even surpassing the oral route. The unique anatomical features of the nasal cavity allow partial direct drug delivery to the brain, circumventing the blood–brain barrier. Systemic absorption through the nasal cavity also avoids the hepatic first-pass metabolism, increasing the systemic bioavailability of highly metabolized entities. Nevertheless, most neurotherapeutics present physicochemical characteristics that require them to be formulated in lipidic nanosystems as self-emulsifying drug delivery systems (SEDDS). These are isotropic mixtures of oils, surfactants, and co-surfactants that, after aqueous dilution, generate micro or nanoemulsions loading high concentrations of lipophilic drugs. SEDDS should overcome drug precipitation in absorption sites, increase their permeation through absorptive membranes, and enhance the stability of labile drugs against enzymatic activity. Thus, combining the advantages of SEDDS and those of the intranasal route for brain delivery, an increase in drugs’ brain targeting and bioavailability could be expected. This review deeply characterizes SEDDS as a lipidic nanosystem, gathering important information regarding the mechanisms associated with the intranasal delivery of drugs loaded in SEDDS. In the end, in vivo results after SEDDS intranasal or oral administration are discussed, globally revealing their efficacy in comparison with common solutions or suspensions.

By dissolving drug molecules in these solutions, a unit dosage form for oral administration can be generated for oral administration. Self-emulsifying drug delivery system (SEDDS) is utilized to address the inadequate bioavailability of poorly soluble and highly permeable drugs, according to the literature. These methods can disseminate and deliver hydrophobic medications as a unit dose form for oral administration in this fashion. SEDDS formulations self-emulsify (micro/nano) after being discharged into the intestinal lumen and coming into contact with the gastrointestinal (GI) fluid. Several factors must be considered to make the oral drug administration difficult, including poor water solubility and limited permeability. Self-emulsifying drug delivery can increase the solubility of biopharmaceutical classification system (BCS) II medicines. The SEDDS is a drug delivery system that enhances the solubility of lipophilic medications. It has risen in popularity over time. Under moderate agitation and subsequent dilution, GI fluids are categorized as hydrophilic liquid mixes that are isotropic. This research looks at a variety of uses as well as recent advancements in SEDDS composition, evaluation, dosage forms, and novel techniques to convert liquid SEDDS to solids. Final Thoughts Determining whether or not it is feasible to construct a BCS Category 2 medication formulation based on SEDDS represents a significant contribution of this effort. Medicines with solubility issues and low and variable bioavailability will benefit from the connected technologies.

Preparation and evaluation of self-microemulsifying drug delivery system of baicalein

The modern drug delivery system of hydrophobic drugs presents a main challenge because of the poor aqueous solubility of such compounds. Self emulsifying drug delivery systems (SEDDS) are usually used to enhance the bioavailability of hydrophobic drugs. SEDDS can be administered orally in soft or hard gelatin capsules and form fine relatively stable oil in water (o/w) emulsions upon aqueous dilution due to the gentle agitation of the gastrointestinal fluids. From time to time so many workers have claimed different rational applications of Self-emulsifying formulation for increcing bioavailability and site-specific targeting of highly lipophilic drugs. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future. The present article gives an overview of the Composition, mechanism, advantages, disadvantages, characterization, recent advancements, patents related information of SEEDS and commercial products approved for oral transmucosal administration.

The current investigation aimed at formulating self-microemulsifying drug delivery system (SMEDDS) to ameliorate oral bioavailability of a hydrophobic functional ingredient, limonene. Solubility test, compatibility test, and pseudo-ternary phase diagrams (PTPD) were adopted to screen the optimal compositions of limonene-SMEDDS (L-SMEDDS). The characteristics of this system assessed in vitro, mainly included determination of particle size distribution, observation of morphology via transmission electron microscopy (TEM), testing of drug release in different dissolution media, and evaluation of stability. The oral bioavailability study in vivo of the formulated limonene was performed in rats with the free limonene as the reference. Compared with the free limonene, the distribution study of L-SMEDDS was conducted in Kunming mice after oral administration. The optimized SMEDDS (ethyl oleate, 14.2%; Cremophor EL, 28.6%; isopropanol, 28.6%; and loaded limonene, 28.6%) under the TEM (about 100nm) was spherical with no significant variations in size/appearance for 30days at 4, 25, and 60°C. In comparison with free limonene, higher than 89.0% of limonene was released from SMEDDS within 10min in different dissolution media. An in vivo study showed a 3.71-fold improved oral bioavailability of the formulated limonene compared to the free limonene. The tissue distribution results showed that limonene predominantly accumulated in the various tissues for the L-SMEDDS compared with the free limonene. Hence, L-SMEDDS could remarkably improve the concentration of limonene in the various organs. These findings hinted that the oral bioavailability of limonene could be improved via an effectual delivery system like SMEDDS.

Background: Poor water solubility of the therapeutic compounds has become a very challenging issue for the delivery of drugs through conventional approaches. Over 40% of newly discovered active compounds also have a lack of water solubility and are lipophilic in nature. One approach for increasing the oral bioavailability of therapeutic agents is to deliver the drug via a self-emulsifying drug delivery system (SEDDS). Although many studies have been carried out, there are few drug products on the pharmaceutical market formulated as SEDDS, confirming the difficulty of formulating hydrophobic drug compounds into such formulations. Objectives: This review aims to describe the SEDDS formulation, its composition, as well as the manufacturing techniques and recently developed formulations, and also highlights an important characterization test for the evaluation of SEDDS. Methodology: Relevant literature was searched in English using different databases, i.e. Google Scholar, PubMed, and Scopus. Results: Within recent years, SEDDS was also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. SEDDS are stable blends of surfactants, oils, solvents, and co-solvents. This system of drug delivery is useful for improving the aqueous solubility of drugs. They could be manufactured by the spray cooling method, the melt granulation process, the lyophilization technique, and by extrusion or spheronization. Various characterization tests, such as zeta potential, viscosity, dispersibility, cloud test, percentage transmittance, etc., could also be performed to confirm the stability of the SEEDS. Conclusion: Recently, many formulations have been developed for the delivery of drugs through the use of SEEDS and have shown increased bioavailability of the drug, as well as many promising outcomes.

Aim: The research aimed to design the glimepiride self-micro emulsifying drug delivery system (SMEDDS) for increased oral bioavailability in albino mice by assessing hypoglycemic efficacy. Materials and Methods: The optimized liquid SMEDDS (L-SMEDDS) prepared by emulsification of Capryol® 90 (oil), Kolliphore® EL (surfactant), and Transcutol® P (co-surfactant) were screened based on their solubility in glimepiride. Adsorption onto Aerosil® 200 Pharma produced solid SMEDDS (S-SMEDDS), and further direct compression was used to manufacture the tablets. The formulations were subjected to droplet size, polydispersity index (PdI), time of emulsification, in-vitro drug release, crystallinity nature, surface morphology, thermal behavior, ex-vivo permeability, and in-vivo hypoglycemic activity in albino mice. Results: The SMEDDS emulsified in less than 30 sec and had an average droplet size of 22.3 nm with a PdI of 0.296. The solid-state analysis revealed that glimepiride was in a molecular dispersion or amorphous form. In-vitro release experiments demonstrated that glimepiride released more efficiently than plain glimepiride. Both L-SMEDDS and S-SMEDDS did not have any significant differences in terms of release. The ex-vivo and in-vivo studies revealed that SMEDDS possess improved permeability and hypoglycemic activity than plain glimepiride. Conclusion: The study proved the combination of lipid-based nanosystems with oral dosage forms improved the oral bioavailability of glimepiride SMEDDS.