Formulation strategies for drug delivery of tacrolimus: An overview

Abstract

Tacrolimus (FK 506) is a potent macrolide lactone immunosuppressive agent used for prophylaxis of organ rejection after transplantation and graft-versus-host disease after bone marrow transplantation in patients. Moreover, tacrolimus is a drug of choice in the treatment of atopic dermatitis for decreasing side effects associated with the use of topical corticosteroids. In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated due to its narrow therapeutic index (between 5 and 15 ng/ml). Tacrolimus has a large inter-/intra-patient variability in pharmacokinetics profile and a poor oral bioavailability because of its poor solubility, P-gp efflux, marked pre-systemic metabolism by CYP3A in the enterocytes and liver first pass effect. Several formulation approaches such as oily solution, solid dispersions, complexation with cyclodextrins, liposomes etc., have been investigated to improve oral delivery of FK 506. In this review, we have discussed various formulation approaches that have been undertaken by various researchers to solve the problems related to the drug delivery of tacrolimus.

Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation

“…When used with hydrophilic substances such as liposomes, tacrolimus becomes highly soluble. 11 Pharmacokinetic study revealed that the use of liposomes as a delivery vehicle increased endocytosis while decreasing systemic exposure and vehicle related toxicity in comparison to non-encapsulated tacrolimus in rats. 12, 13 …”

Chemometric Methods for the Quantification of Crystalline Tacrolimus in Solid Dispersion by Powder X‐Ray Diffractrometry

“…The main focus of formulating the poorly aqueous soluble drug is to present the drug in its molecular form to the absorbing surface, that is, gut mucosa. Any intrinsic or extrinsic factor triggering crystallization of the drug in the formulation can impact an overall absorption and thereby bioavailability of the drug, which is of particular concern to a drug like tacrolimus possessing a narrow therapeutic index (5–15 μg/mL) . Sub‐potent dose of tacrolimus can increase the potential of a graft rejection, whereas overdose can cause dose‐dependent neuro/nephrotoxicity.…”

Design, Characterization, and In Vivo Pharmacokinetics of Tacrolimus Proliposomes

“…Tacrolimus is classified as a class II drug according to the biopharmaceutical classification system (12). Tacrolimus exhibits poor aqueous solubility, P-gp efflux, and extensive presystemic metabolism resulting in low bioavailability following oral administration (13)(14)(15)(16). The reported mean bioavailability is approximately 21% with large intersubject variability.…”