Formulation and Evaluation of Solid Lipid Nanoparticles of a Water Soluble Drug: Zidovudine

Abstract

The drug delivery system using solid lipid nanoparticles (SLN) came into being about two decades ago and since then lot of work has been done in this field.1-5) SLN for oral drug administration are specifically used to target the uptake of the drug by lymphatic system which prevents its first pass metabolism. Lymphatic uptake of drugs follow two routes which include transcellular transport through the enterocyte and phagocytosis of the drugs by Mast cells of payer's patches lining the intestinal mucosa. [6][7][8] The production of this nano particulate system is based on the principle of solidification of lipid nano emulsion.9) The different technologies available for the fabrication of SLN are high shear homogenization, ultrasound, high pressure homogenization (cold homogenization and hot homogenization), solvent emulsification/evaporation and microemulsion method.10) The major excipients used in the development of the SLN are fatty acids, mono, di and triglycerides, phospholipids etc., which are part of the physiological composition and thus are biocompatible to the body. [11][12][13] SLN have been shown to have superior advantages over polymeric nanoparticles, fat emulsion and liposomes.14) SLN can be produced on large scale and are also biocompatible to the body as compared to polymers, the monomeric unit of which are cytotoxic to the body.15,16) SLN exhibit sustained release effect due to the immobility of drug within lipid as compared to the emulsion formulations 17) and also exhibit better physical and chemical stability of drug compared to liposome.18) This delivery system has been extensively used as carriers for proteins, protein drugs, vaccines and lipophilic water insoluble drugs. 19) SLN are potential delivery system for lipophilic drugs where aqueous solubility of the drug is the limiting factor for its absorption. [20][21][22] Moreover, the incorporation of such drugs within SLN is easier due to their affinity for the lipid. On the other hand, entrapment of hydrophilic drug inside the hydrophobic matrix of SLN is a real challenge as the drug has maximum tendency to partition in the water during the fabrication process. Although a few hydrophilic molecules have been incorporated into SLN like thymocratin, 23) insulin, 24) diminazene 25) and thymopentin, 26) lot more scope still remains for the entrapment of hydrophilic drugs into lipid nanoparticles.Zidovudine (AZT), a hydrophilic drug has been used in the present investigation. It belongs to the class of nucleoside reverse transcriptase inhibitor and is used in the treatment of AIDS. This drug has various disadvantages like short biological half life due to extensive first pass metabolism and dose related bone marrow toxicity. AZT is a potential candidate for delivery via lipid based nanoparticulate system as this would help to improve lymphatic uptake, avoid hepatic first pass metabolism and thus reduce the dose requirement and decrease the side effects. 27) Furthermore, sustained drug release would reduce dosing frequency and at the same time ma...

Equilibrium solubility versus intrinsic dissolution: characterization of lamivudine, stavudine and zidovudine for BCS classification

“…In phosphate buffer pH 6.8, the solubility was 24.4 mg mL -1 at 37 °C and 20.3 mg mL -1 at 25 °C. AZT results of this study are in accordance to results presented by Singh and colleagues (2010) (Singh et al, 2010).…”

“…In phosphate buffer pH 6.8, the solubility was 24.4 mg mL -1 at 37 °C and 20.3 mg mL -1 at 25 °C. AZT results of this study are in accordance to results presented by Singh and colleagues (2010) (Singh et al, 2010).In another study, Prakash and colleagues (2008) examined the solubility of antiretroviral drugs, 3TC, d4T and AZT, in different media (purified water, 0.01 M HCl solution, acetate buffer pH 4.5 and phosphate buffer pH 6.8). The results obtained by these authors are presented in Table III.…”

“…Thus, when the drug dose is extremely high or extremely low (for exemple 1.0 mg mL -1 and recommended dose of 0.25 mg or 4.0 mg mL -1 and recommended dose of 1000 mg) a discrepancy between the equilibrium solubility and the IDR may occur. Further, when the drug dose is extremely high, the in vivo absorption may be limited by solubility (Singh et al, 2010).…”

“…Thus, when the drug dose is extremely high or extremely low (for exemple 1.0 mg mL -1 and recommended dose of 0.25 mg or 4.0 mg mL -1 and recommended dose of 1000 mg) a discrepancy between the equilibrium solubility and the IDR may occur. Further, when the drug dose is extremely high, the in vivo absorption may be limited by solubility (Singh et al, 2010).At least 10 points were used for the construction of intrinsic dissolution profiles of drugs. Due to the high rate of dissolution, short intervals were imposed to reach sampling points and obtain meaningful results.…”

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

“…Thus, when the dose is either extremely high or extremely low (for exemple, a drug with solubility of 1.0 g/mL and its dose is 0.25 mg and another drug 4.0 mg/mL and its dose is 1000 mg) a discrepancy between the current solubility classification and the IDR occurs. Furthermore, when the dose is extremely high, the in vivo absorption process may be limited by the solubility (Dezani et al, 2013a;Issa, Ferraz, 2011;Singh et al, 2010;Yu et al, 2004).…”