Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

Abstract

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Keywords: controlled release; drug delivery; drug localization; liquid crystal; lyotropic; surfactants.

Figure 1

Classification of LLCs. Abbreviations: LLC, lyotropic liquid crystal; IPMS, infinite periodic minimal surface.

Figure 2

(A) The mesophases of LLC: i, lamellar phase; ii, hexagonal phase; iii, micellar cubic phase – bcc; iv, micellar cubic phase – fcc (different colors represent the three-dimensional arrangement of the same molecules present in the micellar cubic phases); v, primitive bicontinuous cubic phase; vi, double diamond bicontinuous cubic phase; vii, gyroid bicontinuous cubic phase. (B) Schematic of self-assembly structures corresponding to CPP values. P stands for CPP values. V is the hydrophobic tail volume, a is the hydrophilic head group area and l is the hydrophobic tail length. (C) Possible localization of drugs in the following: i, reverse hexagonal phase; ii, reverse bicontinuous cubic phase (double diamond); iii, reverse bicontinuous cubic phase (primitive). Abbreviations: bcc, body-centered cubic; CPP, critical packing parameter; fcc, face-centered cubic; LLC, lyotropic liquid crystal.

Figure 3

Drug solubilization within the small intestine. Notes: The drugs are localized in lipid droplets possessing multiple layers of LCs on their surface. The layers are then shed from the droplet, forming small unilamellar or multilamellar vesicles. These vesicles are then solubilized into micelles and mixed micelles. Further solubilization would then promote lipid absorption across the intestinal mucosa. Abbreviations: BS, bile salt; DG, diglycerol; FA, fatty acids; LC, liquid crystal; MG, monoglycerol; PL, phospholipid.

Figure 4

Transdermal drug delivery using LCs. Note: Representative primitive bicontinuous cubic phase is shown. Abbreviations: LC, liquid crystal; SC, stratum corneum.