Oily vehicles

Introduction of a second solvent, incompatible with the continuous phase of a normally stable dispersion, produces an unstable condition if the new solvent wets the surface of the solid better than does the original vehicle. The instability induced by the introduction of a oily vehicle to an aqueous dispersion of an organic pigment is exploited commercially in the so-called flushing of pigments from an aqueous liquor into a vehicle. 

Soft gelatin capsules are not an inexpensive dosage form, particularly when compared to direct compression tablets [3]. There is a more intimate contact between the shell and its liquid contents than exists with dry-filled hard gelatin capsules, which increases the possibility of interactions. For instance, chloral hydrate formulated with an oily vehicle exerts a proteolytic effect on the gelatin shell however, the effect is greatly reduced when the oily vehicle is replaced with polyethylene glycol [3]. 

Intramuscular Route. The IM route is frequently used for drugs dissolved in oily vehicles or for those in a microcrystalline formulation that are poorly soluble in water (e.g., procaine or penicillin G). Advantages include rapid absorption (often in under 30 min), the opportunity to inject a relatively large amount of solution, and a reduction in pain and local irritation compared with SC injections. Potential comphcations include infections and nerve damage. The latter usually results from the choice of an incorrect site for injection. 

Drugs that are insoluble at tissue pH, or that are in an oily vehicle, form a depot in the muscle tissue, from which absorption proceeds very slowly. 

Dimercaprol (BAL, British Anti-Lewisite) was developed in World War 11 as an antidote against vesicant organic arsenicals (B). It is able to chelate various metal ions. Dimercaprol forms a liquid, rapidly decomposing substance that is given intramuscularly in an oily vehicle. A related compound, both in terms of structure and activity, is di-mercaptopropanesulfonic acid, whose sodium salt is suitable for oral administration. Shivering, fever, and skin reactions are potential adverse effects. 

The drug is injected as a bolus or infused slowly directly into a vein to produce rapid action. It is also useful for certain irritant and hypertonic solutions, as they are rapidly diluted by the blood. Drugs in an oily vehicle or those which precipitate blood constituents or haemolyze erythrocytes should not be given by this route. 

Zinc-white Paint.—Like white lead, tho oxide of zinc requires to be mixed with an oily vehicle, to be applied in painting. As oxide of zinc does not readily form a saponaceous compound with fate or oils like oxide of lead the paint which is prepared with it and ordinary linseed ofl, does not dry or harden for a long time. This peculiarity was at first one of the principal... 

FIGURE 6.2 Probucol plasma profiles following oral administration (100 mg/kg) to rats in three different oily vehicles peanut oil (LCT, ), miglyol (MCT, A), or paraffin oil ( ). (From Palin, K.J. and Wilson, C.G., J. Pharm. Pharmacol., 36, 641, 1984. With permission.)... 

Ichihashi, T., et al. 1992. Effect of oily vehicles on absorption of mepitiostane by the lymphatic system in rats. J Pharm Pharmacol 44 560. 

If the drug is insoluble in water, suspensions have to be administered. In such cases vehicles like sesame oil, hydroxy-methyl-cellulose or hydroxy-ethyl-cellulose can be used. The selection of the vehicle is a critical issue because of inherent toxicity of the vehicle used frequently for kinetic and metabolism studies (e.g. vehicles which form metabolically oxalic acid). Natural oils such as sesame or com oil can be used. However, it should be checked whether the use of oily vehicles alters the gastrointestinal absorption due to their laxative properties and whether oily vehicles can cause oil granulomas (reaction to oily vehicles in the reticulo-endothelial system) in case of parenteral administration. 

Solutions (ready to use)— preferable aqueous solutions are used but oily vehicles may be used for solubility reasons... 

Following intramuscular (IM) administration, drugs must cross one or more biological membranes in order to enter the systemic circulation. Intramuscular injection is used mainly for drugs and vaccines that are not absorbed orally, for example, aminoglycosides, insulin, and hepatitis vaccine. The IM route is often used for sustained medication and specialized vehicles, such as aqueous suspensions, oily vehicles, complexes and microencapsulation, which has been developed for slow delivery of drugs by this route. ... 

A palatable suspension of the bitter-tasting drug, remoxipride, was developed based on microparticles prepared by spray congealing. Because of the high water solubility of the drug, the microparticles were formulated into an external oil phase. Unfortunately, neither the nature of the wax nor of the oily vehicle was revealed. 

Howard JR, Hadgraft J. The clearance of oily vehicles following intramuscular and subcutaneous injections in rabbits. Int J Pharm 1983 16 31-39. 

Vinardell MP, Vives MA. Plasma creatine kinase activity after intramuscular injection of oily vehicles in rabbits. Pharm Pharmacol Lett 1996 6(2) 54—55. 

There have been suggestions that lipid-soluble dmgs may be absorbed by fat absorption pathways. Certainly, administration of dmgs in an oily vehicle can significantly affect absorption, increasing it in the case of griseo-fulvin and ciclosporin, but decreasing it in the case of vitamin D. 

Ideally, the kinetics of the prodrug and the active moiety should be studied in the same patients or healthy volunteers. It is not possible to provide generally valid guidelines for study design because, as described in the previous sections, many factors may influence the analysis of the data, and consequently the way in which data must be collected. For example, it is certainly very different to study a prodrug such as bacampicillin with a very fast release of ampicillin after oral administration, or the decanoic ester of haloperidol given intramuscularly as a depot preparation in an oily vehicle. 

Poorly soluble drugs for intramuscular administration can be formulated in a non-aqueous vehicle this can have the additional benefit of providing a slow release of the active moiety. Oily vehicles have been used historically the most commonly encountered is sesame oil, and... 

Haloperidol IM (oily vehicle) 1.2% Benzyl alcohol in sesame oil... 

The use of oily vehicles as an approach for the formulation of poorly soluble molecules is discussed in the section Non-aqueous Vehicles . For molecules which possess good oil solubility, a sustained-release profile may also be achievable. The nature of the sustained-release profile will depend to a large extent on the oil/water partition coefficient of the molecule in question. Molecules which are not oil miscible could also be formulated as oily suspensions. The latter will usually result in a longer duration of action, because the drug particles must dissolve in the oily phase prior to partitioning into the aqueous medium (Madan 1985). The use of oily vehicles would not normally be considered as a first-line approach for new formulations, however, because of concerns over allergic reactions to the oils. 

If the desired aqueous solubility is not achievable by any means, then alternatively, an oily solution or emulsion formulation could be considered. These systems rely on the drug partitioning out of the oily phase available in the eye, and are generally not as well tolerated as aqueous based delivery systems. For these reasons, aqueous suspension formulations are probably preferred to oily vehicles, employing very small drug particles to encourage dissolution and drug availability in the eye. 

---