Oily solution

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

The aqueous alkaline extract is heated to ioo° to remove ether and volatile impurities. The solution is then cooled with ice and acidified with 25 per cent sulfuric acid, and the organic acid separated. The water layer is distilled from a 2-1. flask until no more oily solution comes over, The distillate is saturated with salt and the acid layer is separated. This water layer together with the low boiling fraction from distillation of the crude trimethylacetic acid is distilled and the distillate salted out as before. 

Parenteral dose forms include aqueous, aqueous organic, and oily solutions, emulsions, suspensions, and solid forms for implantation. These parenterals need to be sterile and pyrogen-free they are, if possible, buffered close to normal physiological pH and preferably are isotonic with the body fluids. 

The structures of four of the synthetic carotenoids (beta-carotene, canthaxanthin, beta-apo-8 -carotenol, beta-apo-8 -carotenoic acid) are shown in Fig. 8.2. By virtue of their conjugated double bond structure, they are susceptible to oxidation but formulations with antioxidants were developed to minimize oxidation. Carotenoids are classified as oil soluble but most foods require water soluble colorants thus three approaches were used to provide water dispersible preparations. These included formulation of colloidal suspensions, emulsification of oily solutions, and dispersion in suitable colloids. The Hoffman-LaRoche firm pioneered the development of synthetic carotenoid colorants and they obviously chose candidates with better technological properties. For example, the red canthaxanthin is similar in color to lycopene but much more stable. Carotenoid colorants are appropriate for a wide variety of foods.10 Regulations differ in other countries but the only synthetic carotenoids allowed in foods in the US are beta-carotene, canthaxanthin, and beta-8-carotenol. 

A further possibility is the formation of liquid crystals on contact with body fluids at the site of application. The initially applied drug solution interacts with body fluids such as plasma, tears, or skin lipids and undergoes a phase transition into a mono-or multiphasic system of liquid crystals (Fig. 15). For example, oily solutions of reverse micellar solutions of phospholipids, which solubilize additional drug, trans-... 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

Estrogen preparations. Depot preparations for i.m. injection are oily solutions of esters of estradiol (3- or 17-OH group). The hydrophobicity of the acyl moiety determines the rate of absorption, hence the duration of effect... 

Pharmacokinetics Absorption of oral tablets and parenteral oily solutions of progestins is rapid. The hormone undergoes prompt hepatic transformation. 

Mesterolone is a non-17-alkylated derivative which is also has weak activity orally. Testosterone itself has little activity when taken orally and is used sublingually or as an implant. By esterification of testosterone formulations of long-acting testosterone derivatives in oily solutions for intramuscular injection were developed. 

Parenteral administration This route is applicable for drugs which are inactivated by gastrointestinal tract or absorption is poor when given orally or there is a urgency for fast response in small dose. Intramuscular, intravenous, or subcutaneous routes are commonly used. The intravenous injection (in aqueous solution) is introduced directly into the vein by which a rapid response is produced. The subcutaneous injection are given through the layer of skin, while intramuscular injection, introduced through the skin layer deep into the muscle. The nature of intramuscular injection may be in aqueous or oily solution/suspension form. The aqueous solution will be rapidly absorbed as compared to oily solution or suspension. So, the rate of absorption is dependent on the nature of the preparation. 

Further cases in which simple oily solutions or suspensions contributed to higher absorption are cinnarizine [23], phenytoin [24], and lipophilic steroid [25]. 

Hauss et al. [26] investigated the absorption of ontazolast, a poor water-soluble (0.14 pg/mL) LTB4 inhibitor, following oral administration of a few formulations to rats. All the oil-containing formulations markedly improved ontazolast bioavailability, with the most profound effect observed following the emulsion administration. Bioavailability following a nonoily suspension of ontazolast was 0.5%, whereas an oily solution improved bioavailability to 5.3%, and the emulsion formulation caused total bioavailability of 9.6%>. 

Figure 3. CD curves for testosterone phenylpropionate injections with various concentrations of benzyl alcohol a 1.0 ml injection was diluted to 25.0 ml with cyclohexane, (a) 50pl, (b) 200 pi, (c) 600pi benzyl alcohol per 1 ml oily solution. The descending ordinate represents increasing negative ellipticity and the scale divisions are 0.01°. (From Ref. 22).

Caution. In fatty or oily solution it is safe and stable but in alcoholic solution the substance must be handled with the utmost caution. 

Several SVIs are marketed as oily solutions (Table 2). The oil must be of vegetable origin (sesame, olive, or cottonseed oils are most commonly used) because of safety, purity, and biocompatiblity considerations. Oils for injection must meet USP requirements ... 

Oily solutions are prepared by separately sterilizing the solvent, usually using dry heat, and the drug (dry... 

Sesame oil, cottonseed oil, and other vegetable oils are used as vehicles for water-insoluble drugs such as corticosteroids and oil-soluble vitamins. Oily solutions can be administered only by intramuscular injection. 

When exposed to air and light, phenol turns a red or brown color, the color being influenced by the presence of metallic impurities. Oxidizing agents also hasten the color change. Aqueous solutions of phenol are stable. Oily solutions for... 

The low solubility of steroids in water presents a problem in their formulation for ophthalmic use. The requirements of optical clarity preclude the use of oily solutions or suspension and there are many examples of the use of nonionic surfactants as a means of producing clear solutions which are stable to sterilisation. In most formulations, solubilisation has been achieved using polysorbates... 

Chemically pure carbonate of potash is best prepared by the ignition of pure bicarbonate (see below) in iron or (better) in silver or platinum vessels or else by the calcination of pure bitartrate (see TABTaaic Acu>). The iatlec operation furnishes an intimate mixture of the carbonate with charcoal, from which tho carbonate ia extracted by lixiviation with water and filtration. The filtrate is evaporated to dryness (in iron or platinum) and the residue fully dehydrated by gentle ignition. Tho salt is thus obtained as a white porous mass, fusible at a red heat (836 C., Carndlcy) into a colourless liquid, which freezes into a while opaque piass. The dry salt ia very hygroscopic it deliquesces into an oily solution oleum tartar ) in ordinary air. 100 parts of water dissolve—... 

Injections may be aqueous solutions, oily solutions (because of poor aqueous solubility or the necessity for a prolongation of drug activity), aqueous suspensions or oily suspensions. They may be asepti-cally produced or terminally sterilized in their final containers. Those drugs that are unstable in solution may be presented as a freeze-dried (lyophilized) powder. The choice of final packaging should not determine the method of sterilization. 

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