Improving the High Variable Bioavailability of Griseofulvin by SEDDS

Abstract

Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils and surfactants, ideally isotropic, and sometimes containing cosolvents, which emulsify spontaneously to produce fine oil-in-water emulsions when introduced into aqueous phase under gentle agitation.1) Recently, SEDDS have been formulated using medium chain triglyceride oils and nonionic surfactants, the latter being less toxic. Upon peroral administration, these systems form fine emulsions (or microemulsions) in gastro-intestinal tract (GIT) with mild agitation provided by gastric mobility.2,3) Potential advantages of these systems include enhanced oral bioavailability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s) toward specific absorption window in GIT, and protection of drug(s) from the hostile environment in gut. [4][5][6] The process of self-emulsification proceeds through formation of liquid crystals (LC) and gel phases, the properties of which significantly affect the formation of droplets and interface available for partitioning of drug.5-9) Many workers claim various rational applications of SEDDS for delivering and targeting lipophilic drugs (e.g., WIN 54954, 1) N-4472, 10) idebenone, 11) coenzyme Q10, 12) vitamin E, 13) halofantrine, 14) and cyclosporin A. 15) However, very few reports are available of SEDDS of water insoluble or poorly soluble hydrophobic compounds. Therefore the concept of using griseofulvin in SEDDS was considered for the present study, where the drug is present in solution form.Griseofulvin is an antifungal agent first isolated from a Penicillium spp. in 1939. It is effective after oral ingestion and reaches the skin and hair. It is deposited primarily in keratin precursor cells. Ingestion with a heavy meal and reduction in particle size enhances the absorption of griseofulvin.16) Griseofulvin systematic (IUPAC) name is (2S,6ЈR)-7-chloro-2Ј,4,6-trimethoxy-6Ј-methyl-3H,4ЈH-spiro[1-benzofuran-2,1Ј-cyclohex[2]ene]-3,4Ј-dione (Fig. 1), and its formula is C 17 H 17 ClO 6 with molecular weight 352.766 g/mol. The compound is insoluble in water (8.64 mg/l). It has a logP/hydrophobicity 2.15 (partition system octanol/water), and its pK a /isoelectric point is not available.17) Griseofulvin inhibits fungal mitosis by disrupting the mitotic spindle through interaction with polymerized microtubules. 18)Griseofulvin is administered orally. Its microcrystalline and ultramicrocrystalline forms are available as tablets. The microcrystalline form also comes in a pediatric suspension form. The typical dose of microcrystalline form is 500-1000 mg/d. Ultramicrocrystalline form is administered at doses of 330-990 mg/d. 19) Since the bioavailability of poorly water-soluble drugs can be influenced by interactions with food or by the physicochemical conditions in the gastrointestinal (GI) tract, 20) oral preparation of griseofulvin is commonly prescribed to be administered according to a fixed dosing schedule. The oral bioavailability of griseofulvin is highly varia...

Development and Evaluation of Novel Self-Nanoemulsifying Drug Delivery Systems Based on a Homolipid from Capra hircus and Its Admixtures with Melon Oil for the Delivery of Indomethacin

“…The solubility of hydrophobic drugs and therefore their bioavailability are improved in such systems by selective dissolution/partitioning in the oily component [31]. Particle sizes in such systems are of the order of 100 nm or less [9, 11, 32]. Stability from precipitation on dilution is a critical design parameter which depends on the solubility of drug in various formulation components [9], particularly in the oil.…”

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“…Moreover, SEDDS is easy to formulate and can be easily administered in the form of soft gelatin or hard gelatin capsules. SEDDS has become favorite formulation strategy for poorly water-soluble and poorly bioavailable drugs not only in research fraternity [11][12][13][14][15][16][17][18][19][20][21] but is also accepted by pharmaceutical industries at large. To name a few, Sandimmune ® and Sandimmune Neoral There has been extensive research on the materials used for preparing SEDDS.…”

Self-emulsifying therapeutic system: a potential approach for delivery of lipophilic drugs

“…Self-emulsifying powder formulation (SE powder formulation) Arida et al (2007) formulated an SE powder formulation in order to enhance the dissolution and absorption of the poorly water-soluble drug griseofulvin. Capmul GMO-50, poloxamer and myvacet were used as surfactants and co-surfactants.…”