Issue link: https://www.e-digitaleditions.com/i/678483
Tablets & Capsules May 2016 43 consider including simulated gastric and intestinal fluid, which includes lipases and bile salts, because the neat lipid system only generates an emul- sion under biological conditions. forms under simulated gastric condi- tions. It is important to understand the nature of a proposed SEDDS sys- tem before designing in vitro testing. For example, if an API were dissolved in a neat lipid, you would need to Solid lipid formulations Higher-molecular-weight lipids, which are solid at room temperature, may also be employed in lipid formu- lations. Typically, these lipids are melted and the API is dissolved in the liquefied lipid while heating. It's also possible to formulate a solid dis- persion by melting the lipid and the API together. The most common methods of generating a solid disper- sion with lipids are spray congealing, hot-melt granulation, and hot-melt extrusion. In these formulations, it is desirable that the melting point of the lipid materials be as close as pos- sible to the melting point of the API. In certain cases, however, the API's melting point can be higher and the API will still dissolve in the molten lipid(s). Additionally, you must not exceed the degradation temperatures of the lipid excipients during the melt formation. Once the API is melted with the lipids, the materials should be rapidly cooled to solidify them to ensure the API is dispersed amorphously throughout the lipid matrix. One form of solid lipid formulations is solid lipid nano-particles (SLNs). These nano-sized lipid carrier parti- cles are generated by melting that is followed by high-pressure homoge- nization and subsequent cooling. SLNs have been reported to provide a means for controlling drug delivery, enhancing bioavailability through both dissolution modification and enhanced tissue distribution, and tar- geting drug delivery through various application routes [5]. SLNs have been proposed as potential carriers for cyclosporin A, insulin, calcitonin, and somatostatin. Formulation of proteins in SLNs can improve the stability of the protein, reduce prote- olytic degradation, and provide sus- tained release of the protein [6]. Conclusion The majority of NCEs exhibit solu- bility and/or permeability challenges. Functional lipid formulations, including SEDDS, can overcome these chal- lenges. Specific APIs can be dissolved in neat lipids or formulated in a Figure 2 Example of a pseudo-ternary phase diagram [2] 0 10 20 30 40 50 60 70 80 90 100 Gel Emulsion Microemulsion Microemulsion 1:1 PG monolaurate/ PG dilaurate % w/w surfactant % w/w lipid mixture Water % w/w water Poly-ethoxylated castor oil 100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 0 TAble 1 Lipid formulation classification system [1] Emulsion type Typical Type I Type II Type IIIA Type IIIB composition (%) Triglycerides or 100 40 to 80 40 to 80 < 20 mixed glycerides Surfactants - 20 to 60 20 to 40 20 to 50 Hydrophilic - - 0 to 40 20 to 50 cosolvents Particle size of Coarse 100 to 250 100 to 250 50 to 100 dispersion (nm) Significance of Limited Solvent Some loss of Significant phase aqueous dilution importance capacity solvent capacity changes and unaffected potential loss of solvent capacity Significance of Crucial Not crucial but Not crucial but Not required digestibility requirement likely to occur may be and not likely inhibited to occur