Excipient microemulsion

Altria, K. D. (1999). Application of microemulsion electrokinetic chromatography to the analysis of a wide range of pharmaceuticals and excipients.. Chromatogr A 844, 371—386. 

In pharmaceutics, therefore, simple and effective methods and procedures are needed to characterize the interactions of drugs with pharmaceutical excipients (polysaccharides, cyclodextrins, etc.) and vehicle systems (micelles, microemulsions, and liposomes) in order to optimize the load of vehicle systems with the drugs. 

Part II starts with the possibilities of ACE for characterizing the relevant physicochemical properties of drugs such as lipophilicity/hydrophilicity as well as thermodynamic parameters such as enthalpy of solubilization. This part also characterizes interactions between pharmaceutical excipients such as amphiphilic substances (below CMC) and cyclodextrins, which are of interest for influencing the bioavailability of drugs from pharmaceutical formulations. The same holds for interactions of drugs with pharmaceutical vehicle systems such as micelles, microemulsions, and liposomes. 

Excipients offer several possibilities and mechanisms. For microemulsions, Cremophor RH 40, Cremophor EL, and Solutol HS 15 act as surface active solubilizers in water and form the structures of micelles. The micelle that envelops the active substance is so small that it is invisible, or perhaps visible in the form of opalescence. Typical fields of application are oil-soluble vitamins, antimycotics of the miconazole type, mouth disinfectants (e.g., hexiditin), and etherian oils or fragrances. Solutol HS 15 is recommended for parenteral use of this solubilizing system and has been specially developed for this purpose. 

Various excipients have been used as solubilizers for BCS class II and class IV drugs. Cyclodextrins provide a prime example of the use of excipients as solubilizers, and have been discussed in detail in a separate chapter. Various surfactants have also been used to create emulsion-/microemulsion-type formulations. These have been discussed in a separate chapter as well. 

Lipid-based formulations offer a large variety of optional systems. They can be made as solutions, suspensions, emulsions, self-emulsifying systems and microemulsions. Moreover, it is possible to form blends that are composed of several excipients they can be pure triglyceride (TG) oils or blends of different TG, diglyceride (DG) and monoglyceride (MG). In addition, different types of surfactants (lipophilic and hydrophilic) can be added, as well as hydrophilic co-solvents. Lack of enhanced absorption when one of the above key formulations is tested does not necessarily indicate the effectiveness of alternative lipid-based formulations, and their suitability has to be examined. 

Emulsions and Microemulsions, p. 1548. Excipients for Pharmaceutical Dosage Eorms, p. 1609. 

The range of complexity of solubilized oral formulations filled into a capsule varies from a simple one-excipient formulation such as PEG 400 or a long-chain triglyceride, to complex microemulsion preconcentrates which contain oil, cosolvent, and surfactant excipients. The preferred water-soluble organic solvents... 

As a guide to solubilized oral formulation drug development, the following examples illustrate the formulation philosophy of simple to complex . Starting with one-excipient formulations to complex microemulsion preconcentrates. 

The highest level of complexity of lipid-based formulations in currently marketed products can be illustrated by three cyclosporin A products, which contain mixtures of five or six excipients and are microemulsion preconcentrates. Gengraf , Neoral , and Sandimmune soft gelatin capsules are all stored at room temperature. 

A formulation approach applied to the cyclic peptide SKF 106760 (3) employed a water-in-oil microemulsion (composition Captex 355/Capmul MCM/Tween 80/Aqueous 65/22/10/3, %w/w) to enhance intestinal absorption, improving bioavailability after i.d. administration in rats from 0.5% to 27% [135], A modest improvement in oral bioavailability (from 5-19%) of another cyclic peptide, DMP 728 (5) has been achieved in dogs using the fatty acid excipient sodium caprate [136]. 

The phenomenon of microemulsification is mainly governed by factors such as (1) nature and concentration of the oil, surfactant, co-surfactant and aqueous phase, (2) oil/surfactant and surfactant/co-surfactant ratio, (3) temperature, (4) pH of the environment and (5) physicochemical properties of the API such as hydrophilicity/lipophilicity, plformulating microemulsions. From a pharmaceutical perspective, one of the most important factors to be considered is acceptability of the oil, surfactant and co-surfactant for the desired route of administration. This factor is very important while developing micro emulsions for parenteral and ocular delivery as there is only limited number of excipients which are approved for the parenteral and ocular route. In Chapter 3 of this book a more general overview of formulating microemulsions is given and formulation considerations with respect to the components of microemulsions used in pharmaceutical applications are discussed below. 

Although numerous applications of microemulsions have been described, there are still many avenues remaining to be explored. There is still a need for better excipients having acceptability for parenteral and ocular route. The excipients like caprylic acid mono-,... 

In recent years there has been an increased interest in the utility of lipid-based delivery systems to enhance oral bioavailability (4). It is generally known that membrane permeability is directly correlated to a drug s water-lipid partition coefficient however, the systemic availability of highly lipophilic drugs is impeded by their low aqueous solubility. In an effort to improve this solubility-limited bio-availabiliy,formulators have turned to the use of lipid excipients to solubilize the compounds before oral administration. Several formulations are currently on the market, for example, Sandimmun/Neoral (cyclosporin microemulsion), Norvir (ritonavir), and Fortovase (saquinavir)... 

The selection of the components to be used in the microemulsion is a very critical step. The pharmaceutical acceptability of the components and their toxicity issues must be considered. A large number of oils and surfactants are available, but their use in the microemulsion formulation is restricted due to their toxicity, incompatibility, and stability. Components that are used for the formulation of microemulsion should be biocompatible, nontoxic, and clinically acceptable. Emulsifiers should be used in an appropriate concentration range that will result in mild and nonaggressive microemulsion. The selection of generally regarded as safe (GRAS) excipients should always be emphasised. " ... 

Microemulsions are transparent systems of two immiscible fluids, stabilized by an interfacial film of surfactant or a mixture of surfactants, frequently in combination with a cosurfactant. These systems could be classified as water-in-oil, bicontinuous, or oil-in-water type depending on their microstructure, which is influenced by their physicochemical properties and the extent of their ingredients. - SMEDDSs form transparent microemulsions with a droplet size of less than 50 nm. Oil is the most important excipient in SMEDDSs because it can facilitate self-emulsification and increase the fraction of lipophilic drug transported through the intestinal lymphatic system, thereby increasing absorption from the gastrointestinal tract. Long-chain and medium-chain... 

Uses Excipient, coemulsifier, solubilizer, bioavailability enhancer, vehicle for pharmaceuticals (topicals, injectables, orals, nasals, sprays, emulsions, hard shell capsules, soft gel capsules), cosmetics, veterinary preps. cosurfaclant in microemulsions coemulsifier, penetrant for topical emulsions Features Hydrophilic... 

---