The attempts to oral delivery of lipids can be challenging. Self-emulsifying drug delivery system (SEDDS) plays a vital role to tackle this problem. SEDDS is composed of an oil phase, surfactants, co-surfactants, emulsifying agents, and co-solvents. SEDDS can be categorized into self-nano-emulsifying agents (SNEDDS) and self-micro-emulsifying agents (SMEDDS). The characterization of SEDDS includes size, zeta potential analysis, and surface morphology via electron microscopy and phase separation methods. SEDDS can be well characterized through different techniques for size and morphology. Supersaturation is the phenomenon applied in case of SEDDS, in which polymers and copolymers are used for SEDDS preparation. A supersaturated SEDDS formulation kinetically and thermodynamically inhibits the precipitation of drug molecules by retarding nucleation and crystal growth in the aqueous medium. Self-emulsification approach has been successful in the delivery of anti-cancer agents, anti-viral drugs, anti-bacterial, immunosuppressant, and natural products such as antioxidants as well as alkaloids. At present, more than four SEDDS drug products are available in the market. SEDDS have tremendous capabilities which are yet to be explored which would be beneficial in oral lipid delivery.
Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.
In neurodegenerative disorders, crossing the blood-brain barrier to achieve higher brain uptake of drugs has attracted considerable interest of researchers in recent years. The present approach is designed with a hypothesis that polyamidoamine (PAMAM) dendrimer can be suitable for better brain delivery of donepezil (DZ) utilizing the conjugation strategy. Amine-terminated 4.0 G PAMAM dendrimers (utilizing ethylenediamine core) were synthesized and characterized by different spectroscopic methods (1H and 13C NMR, UV–vis, Fourier transform infrared, electrospray ionization mass). The synthesized PAMAM dendrimer was then conjugated with DZ-ester and finally DZ (ester)-PAMAM conjugate (PDZ) was prepared. The chemical shifts of −CHO (δ = 9.92) and O–CH3 (δ = 3.153) in 1H NMR spectrum confirmed the synthesis of PDZ. The percent drug conjugation of DZ was approximately 26%, and 16 DZ molecules were conjugated with each PAMAM molecule. The size and ζ-potential observed of PDZ conjugate were 122 ± 1.88 nm and 0.434 ± 0.322, respectively. In vitro release studies suggested that DZ release was in a sustained fashion until 120 h at physiological pH conditions. The in vitro acetylcholine esterase (AChE) inhibition activity of PDZ formulation was significantly higher (p < 0.05) than that of the DZ alone at 1 μM dose. In the in vivo studies, the brain uptake of PDZ was quite higher than that of DZ following intravenous administration in Sprague-Dawley rats. The plasma drug concentration studies resulted into improved pharmacokinetic parameters. Half-life (t 1/2), volume of distribution (V d), and clearance were found to be 5.75 ± 0.41 h–1, 0.135 ± 0.02 L, and 0.016 ± 0.0021 L/h, respectively, in the case of PDZ formulation and 1.09 ± 0.10 h–1, 0.172 ± 0.016 L, and 0.108 ± 0.014 L/h, respectively, in the case of DZ solution. The improved half-life and 4-fold increase in brain uptake was observed in the case of the dendrimer-conjugated formulation, which suggested that the synthesized conjugates provide significantly higher DZ brain delivery. The prepared PDZ-conjugated formulation improved AChE inhibition in vitro and the brain delivery in vivo. This strategy may be explored further for better delivery of DZ to the brain.
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