Dispersing biopharmaceutics

Gershanik, T. and Benita, S. (2000), Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur. J. Pharmaceutics and Biopharmaceutics, 50, 179-188. 

The first commercial formulation of cyclosporin (Sandimmun) contained drug, LCT, ethanol, and polyglycolized LCT administered as either an oral solution/dispersion in water or milk or filled into a soft gelatin capsule. The soft-gel formulation produced a crude oil in water emulsion on capsule rupture in situ. The biopharmaceutical performance of the Sandimmun formulation, however, was relatively poor, because absorption was variable, incomplete (=30%), and affected by food [63-67],... 

Oliver, R., Jones, A., and Rowland, M., A whole-body physiologically based pharmacokinetic model incorporating dispersion concepts Short and long time characteristics, Journal of Pharmacokinetics and Biopharmaceutics, Vol. 28, No. 1, 2001, pp. 27-55. 

Ostrander, K. D., H. W. Bosch, and D. M. Bondanza. 1999. An in-vitro assessment of a NanoCrystal be-clomethasone dipropionate colloidal dispersion via ultrasonic nebulisation. Eur. J. Pharmaceut. Biopharmaceut. 48 207-215. 

De Zordi, N., Moneghini, M., Kikic, 1., Grassi, M., Del Rio Castillo, A.E., and Solinas, D. Applications of snpercritical finids to enhance the dissolution behaviors of furosemide by generation of microparticles and solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics 81 (2012) 131-141. 

Using solids, a double emulsion of solid in oil in water (s/o/w) can be prepared, in which the internal solid phase and external aqueous phase are separated by an oil layer. Initially, the solid pharmaceuticals or biopharmaceuticals are dispersed in the polymer solution to form a primary emulsion. Then the dispersion is introduced into a large volume of aqueous solution containing emulsifying agent, such as PVA or PEG. 

Lidocaine is added by dehquescing lidocaine crystals and levomenthol together. The eutectic mixture is than emulsified in an aqueous gel. The biopharmaceutic advantage of this principle is that a molecular dispersion of the lipophilic lidocaine base in a hydrophihc preparation is formulated. 

The particle size of solid substances of both excipients and active substances is important not just for biopharmaceutical properties (see Sect. 12.3.2) but also for the physical and chemical properties of cutaneous preparations. If the solid is dispersed in a liquid base, the particles must be sufficiently fine to obtain a physically stable suspension (see Sect. 18.4.2). However decrease of particle size may increase the rate of degradation. Additionally processing small particles may lead to agglomerates. 

Solid dispersion is defined as one type of method to produce an amorphous compound by incorporating a hydrophobic drug into a hydrophilic carrier (Chiou and Riegelman 1971). It is one of the most studied methods to solubilize and to enhance dissolution rate of biopharmaceutical classification system (BCS) class 2 compounds. For instance, a solid dispersion of ritonavir (Law et al. 2001), ER-3421 (a dual 5-lipoxygenase/cyclooxygenase inhibitor Kushida et al. 2002), was found to have a much higher dissolution rate than the crystalline counterpart and resulted in higher area under curve (AUC) and Cmax in the in vivo study. 

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