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THE PHARMA REVIEW (NOVEMBER - DECEMBER 2011)

Handling Poorly Bioavailable Drugs Using Nanoemulsifying Drug Delivery Systems

Bhupinder Singh*, Shantanu Bandyopadhyay, Sarwar Beg and OP Katare

Introduction: Oral delivery of more than over one-half of the drug compounds through gastrointestinal (GI) tract gets thwarted owing to their high lipophilicity and consequently, poor aqueous solubility. Oral bioavailability of such drugs, being primarily a function of their solubility and dissolution, tends to exhibit inadequate magnitude with high intra- and inter-subject variability. Besides, oral bioavailability also depends upon a multitude of other drug factors such as stability in GI fluids, intestinal permeability, resistance to metabolism by cytochrome P450 family of enzymes present in gut enterocytes and liver hepatocytes, and interaction with efflux transporter systems like P-glycoprotein (P-gp). Figure 1 explicitly illustrates the mechanisms of the physiological pathways through which the bioavailability of a drug from the conventional formulations tends to get impeded.

 
Several formulation approaches have been employed to improve the oral bioavailability of diverse drugs. Amongst these, oral lipid-based DDS have proved their immense potential in improving the poor and inconsistent drug absorption of many poorly water-soluble drugs, especially following their administration after meals.
 

Self-emulsifying drug delivery systems (SEDDS) are relatively newer lipid-based technological innovations with immense promise in oral bioavailability enhancement of drugs. These formulations have shown to reduce the slow and incomplete dissolution of a drug, facilitate the formation of its solubilized phase, increase the extent of its transportation via intestinal lymphatic system, and bypass the P-gp efflux, thereby augmenting drug absorption from the GI tract. Figure 2 specifically illustrates the lymphatic pathways thorugh which these self-emulsifying formulations are known to carry the drug from the GI mucosa to systemic circulation.

 

 

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