Microemulsion formulation for enhanced absorption of poorly soluble drugs

Kawakami, Kenji; Yoshikawa, Tomohiro; Moroto, Yasushi; Kanaoka, Eri; Takahashi, Kazuhiro; Nishihara, Yoko; Masuda, Kazuyoshi

doi:10.1016/s0168-3659(02)00049-4

Cited by 249 publications

(117 citation statements)

References 24 publications

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“…A greater monophasic zone was obtained for the system composed of IPM and MDG in 2 : 1 ratio, and its properties were studied in detail. The phase behavior of the present system exhibited similarity with those reported by Kawakami et al 22) Very small o/w microemulsion zones have also been reported for the water/IPM/polysorbate 80/sorbitol and water/IPM/phospholipid/alkanol systems. 23,24) The o/w microemulsion region increased as the ratio of IPM/MDG decreased from 4 to 2.…”

Section: Resultssupporting

confidence: 89%

Formulation and Physicochemical Characterization of Microemulsion System Using Isopropyl Myristate, Medium-Chain Glyceride, Polysorbate 80 and Water

Natesan

Ghosal

Acharya

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Microemulsions are isotropic and thermodynamically stable dispersed micro-heterogeneous systems composed of water, oil and amphiphile.1) Their stability and unique solubilization properties have drawn attention for their use as vehicles for drug delivery. Microemulsions have the ability to protect labile drugs, control their release, increase their solubility and bioavailability and reduce patient variability. It has been proven possible to formulate preparations suitable for different routes of administration viz., oral, topical, ocular, pulmonary and intravenous. Microemulsion contains nanometer-sized droplets of oil or water. If the droplets are non interacting the resulting microemulsion will be low in viscosity. On other hand high viscosity and optically clear (microemulsion gel) microemulsions results due to the interaction of cylindrical or wormlike micelles in microemulsion formulations. Microemulsion systems containing lecithin and low water content leads to the formation of microemulsion gel and the utility of the resulting gels have been reported to deliver the drugs through skin. 2,3)Although various types of microemulsions have been reported as being nontoxic, but microemulsion systems composed of regulatory approved excipients for pharmaceutical uses are limited. The choice of oil is limited to medium chain glycerides or fatty acid esters such as isopropyl myristate (IPM), isopropyl palmitate and ethyl or methyl esters of lauric, myristic and oleic acid.2) Uses of pure plant oils have also been reported in recent literature.4-7) Microemulsification of most widely used oil IPM for topical application has been achieved by using lecithin, polyoxyethylene sorbitan n-acyl esters (polysorbate 85, 80, 60, 40), sodium bis-2-ethyl hexyl sulphosuccinate (AOT), sucrose esters, polyoxyethylene (4) lauryl ether, C(12) Eo(8) as surfactants and short chain alcohols (ethanol, propanol, butanol), amines, alkanoic acid, poly ethylene glycol alkyl ethers, sorbitol, sucrose, sucrose ester, propylene glycol, lysolecithin, 2-acyl lysolecithin, mono alkyl phosphate as co-surfactants. 2,[8][9][10][11][12][13][14] In respect of convenience of formation and use, the oil IPM is better choice in comparison with other physiologically tolerable oils. 13)According to reports, medium chain fatty acids, mono-, di-, and tri-glycerides, particularly caprylic/capric mono-/diglycerides have been used independently in mixed micelle, emulsion and microemulsion formulations and as absorption enhancers for a number of drugs, since they have been found to be physiologically well tolerated.15) Further, mono-/diglycerides or polyol fatty acid esters have also been used as a permeation enhancer. 16,17) In view of the above-mentioned prospects, more investigations on micelle and microemulsion formulation using glycerides of the above categories is warranted.In the present study, IPM has been used as oil phase with poloysorbate 80 (polyoxyethylene sorbiton mono oleate) and caprylic/capric mono-/di-glycerides (MDG) as surfactant and co-surfactan...

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Section: Resultssupporting

confidence: 89%

Formulation and Physicochemical Characterization of Microemulsion System Using Isopropyl Myristate, Medium-Chain Glyceride, Polysorbate 80 and Water

Natesan

Ghosal

Acharya

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Transient negative interfacial tension and fluid interfacial film is rarely achieved by the use of a single surfactant, usually necessitating addition of a co-surfactant. The presence of co-surfactant decreases the bending stress of the interface and allows the interfacial film sufficient flexibility to take up different curvatures required to form a nanoemulsion over a wide range of compositions (20). Thus, the co-surfactant selected for the study was Transcutol-P with the HLB value of 4.2.…”

Section: Resultsmentioning

confidence: 99%

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

Baboota¹,

Shakeel²,

Ahuja³

et al. 2007

Acta Pharmaceutica

254

147

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs to reduce pain and inflammation (1). Celecoxib (CXB), a selective cyclo-oxygenase-2 (COX-2) inhibitor, has been recommended orally for the treatment of arthritis and osteoarthritis (2). Long-term oral administration of CXB causes serious gastrointestinal side effects (2). Furthermore, poor aqueous solubility of CXB limits its formulation as topical dosage forms. Therefore, an improved CXB formulation with a high degree of permeation could be useful in the treatment of locally inflamed skin and inflammatory and painful states of the body, like bones, ligaments, etc. Topical vehicle systems can modify drug permeation through the skin but many dermal vehicles contain chemical enhancers and solvents to achieve these goals (3). The use of these chemical enhancers may be harmful especially in chronic applications, since many of them are usually irritants. It is therefore desirable to develop a topical vehicle system, that does not necessitate the The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The in vitro skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (J ss ), permeability coefficient (K p ) and enhancement ratio (E r ) was observed in nanoemulsion formulations T1 and T2 (p < 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% (m/m) of CXB, 10% (m/m) of oil phase (Sefsol 218 and Triacetin), 50% (m/m) of surfactant mixture (Tween-80 and Transcutol-P) and 40% (m/m) water. The anti-inflammatory effects of formulation T2 showed a significant increase (p < 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB.

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“…DPG was very difficult to be solubilized into the non-ionic micelles using a single non-ionic surfactant. 24) Certain mixture of non-ionic surfactants has been reported to enhance the solubilization of water in water-in-oil microemulsion.…”

Section: Resultsmentioning

confidence: 99%

Formulation Design of Self-Microemulsifying Drug Delivery Systems for Improved Oral Bioavailability of Celecoxib

Natesan

Ray

Ghosal

et al. 2004

Biological & Pharmaceutical Bulletin

145

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Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide, is a specific cyclooxygenase-2 (COX-2) inhibitor with no inhibition of cyclooxygenase-1 at therapeutic doses. It is being used successfully for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, familial adenomatous polyposis and primary dysmenorrhea. 1,2) Celecoxib also demonstrated significant chemopreventive activity in colon carcinogenesis, ultraviolet B radiation (UVB) induced skin cancer and breast cancer. [3][4][5] Celecoxib is weakly acidic (pK a is 11.1) and hydrophobic (Log P is 3.5) and its low aqueous solubility (3-7 mg/ml) contributes to high variability in absorption after oral administration. 6)The molecule exists in three polymorphic forms and its solid-state interconversion between the forms at ordinary temperatures has not been observed. It is isolated as agglomerates of long needle-shaped crystals, which exhibit cohesiveness, low bulk density and compressibility, and poor flow properties that impart complications in it's processing into solid dosage forms.7) According to biopharmaceutical classification system, celecoxib is classified as a low solubility and high permeability drug. 6) Therefore, the particle size of celecoxib influences the content uniformity, dissolution and bioavailability of the product. The t max of celecoxib is about three hours after oral administration. Rapid onset of action is necessary to provide fast pain relief in the treatment of acute pain. Therefore, it is necessary to enhance the aqueous solubility and dissolution rate of celecoxib to obtain faster onset of action, to minimize the variability in absorption and improve its overall oral bioavailability. This can be achieved by formulating the drug in lipid-based systems.Among the lipid-based systems, self-microemulsifying drug delivery system (SMEDDS) is a promising technology to improve the rate and extent of the absorption of poorly water-soluble drugs. [8][9][10][11][12][13][14][15] The clinical usefulness of the SMEDDS is evident from the commercially available formulations containing cyclosporin A, ritonavir and Saquinavir. 16,17) SMEDDS are comprised of mixture of drug, oil, surfactant(s) and/or co-solvents which form fine oil in water and/or water in oil microemulsions upon dilution with aqueous medium or in vivo administration. SMEDDS enhances the bioavailability of poorly water-soluble drugs through solubilization in the excipient matrix or interface and dispersion in the gastrointestinal tract. Relatively small size of the dispersed oil droplets in nanometer range and very high surface area to volume ratio are advantages of the microemulsion. These characteristics result in faster drug release from microemulsion in a reproducible manner, which can be designed further to make the release characteristics independent of the gastro intestinal physiology and the fed/fasted state of the patient. 8,[18][19][20] In this study, we have developed an optimized formulation using a self-microemulsifying system in...

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Microemulsion formulation for enhanced absorption of poorly soluble drugs

Cited by 249 publications

References 24 publications

Formulation and Physicochemical Characterization of Microemulsion System Using Isopropyl Myristate, Medium-Chain Glyceride, Polysorbate 80 and Water

Formulation and Physicochemical Characterization of Microemulsion System Using Isopropyl Myristate, Medium-Chain Glyceride, Polysorbate 80 and Water

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

Formulation Design of Self-Microemulsifying Drug Delivery Systems for Improved Oral Bioavailability of Celecoxib

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