Pharmaceuticals progesterone

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

Klang, V., Matsko, N., Zimmermann, A.M., Vojnikovic, E. and Valenta, C. (2010) Enhancement of stability and skin permeation by sucrose stearate and cydodextrins in progesterone nanoemulsions. International Journal of Pharmaceutics, 393, 152—160. 

In certain specific cases either the pure pharmaceutical substance or dosage forms are quantitatively converted to free compound. This conversion to free compound is quantitative and hence forms the basis of gravimetric analysis. A few typical examples belonging to this category are, namely progesterone suspension sterile, progesterone tablets, sodium lauryl sulphate, mephobarbital tablets and sorbitan monooleate. 

The development of a simple fast-scan polarographic method for the determination of the A4-3-ketosteroid flurandrenolone in pharmaceutical preparations has been reported [134]. The polarographic peak due to the reduction of the carbon-fluorine bond is measured in ointments and creams to determine concentrations as low as 0.01 % w/w. Pulse polarographic procedures have been described for progesterones [135], A4-3-ketosteroids [136], hydrocortisone [137], and flucytosine [138] in pharmaceutical preparations. Recent studies have illus-... 

In vitro skin permeation studies in a hydrodynamically well-calibrated skin permeation cell (Figure 4) demonstrated that simple pharmaceutical excipients, like capric acid (a saturated straight-chain fatty acid), can substantially enhance the trandermal permeation rate of progesterone. The time lag is significantly re-... 

As indicated earlier, plant products can be useful as starting materials for the semisynthetic preparation of other drugs. An important example in this regard is the Mexican yam, which produces a steroid precursor (diosgenin) vital to the synthesis of steroidal hormones used in oral contraceptives (i.e., progesterone). The availability of diosgenin eliminates numerous expensive steps in the organic synthesis of the basic steroid molecule. It was this discovery that contributed to the development of the pharmaceutical company Syntex (now a subsidiary of Hoffman LaRoche) and the development of the first birth control pill. 

The most viable method for obtaining larger amounts of steroid hormones is to start with some readily available natural product with a structure that is similar to a steroid and convert it to the desired compound. Russell Marker, a professor at Pennsylvania State University, developed such a method to prepare progesterone from diosgenin, a material that is readily available from Mexican yams. His synthesis is outlined in Figure 28.9. However, he could not interest a major pharmaceutical company in his process, so in 1944 he founded his own company, Syntex, in Mexico City to develop it. 

With the increasing interest in natural source antioxidants, such as tocopherols, and the use of both stigmasterol and (3-sitosterol as raw materials for the production of progesterone and esterone by the pharmaceutical industry, it is likely that deodorizer distillates will continue to be an important by-product for some vegetable oil processors. 

Phytosterols are found in most common vegetable oils. For example, soybean oil, one of the most commonly consumed oils, is reported to contain approximately 0.36% sterols and 0.124% tocopherols (15). The effect of phytosterols on the reduction of serum cholesterol has been attributed to the possible inhibition of intestinal reabsorption of circulating cholesterol. The saturated version of sterols, stanols, is reported to be more readily metbolized, and this has led to the development of nutritional supplements and it is used commercially in food products such as margarines. The main stanol reported for this application is sitostanol, a saturated derivative of sitosterol. Sterol and cholesterol are used by the human body to synthesize important hormones such testosterone and progesterone, which are used also in many pharmaceutical applications. 

Variations in lattice energies between amorphous and crystalline forms can significantly influence a drug s aqueous solubility, and increases of several hundredfold were observed for morphine and benzimidazole derivatives. Furthermore, a substance may exist in more than one crystalline form, such as chloramphenicol, dehydroepiandrosterone (DHEA), progesterone, sul-fathiazole, carbamazepine, cortisone, or prednisolone, to name a few. Polymorphic transformations, routinely observed for pharmaceuticals, are structural differences resulting from different crystal arrangements of molecules in the solid state. Although thermodynamic differences between polymorphs disappear once dissolved. 

A number of pharmaceutical microencapsulated products are currently on the market, such as aspirin, theophylline and its derivatives, vitamins, pancrelipase, antihypertensives, potassium chloride, progesterone, and contraceptive hormone combinations. ° ... 

Another variant on hormone replacement therapy involves using aU three types of sex steroid in parallel, starting from the argument that during the fertile period all three are sjmthesized by the ovary (7). A natural version of this therapy uses estradiol, testosterone (with or without dehydroepiandrosterone), and progesterone in an appropriate pharmaceutical form (for example micro-nized), so that absorption is attained without the need for 17-substitution. This approach naturally avoids some of the undesirable effects of the synthetic steroids, and has been stated to improve menopausal depression and anxiety. However, the adverse effects of all three types of component can be experienced. 

The major use of sesame oil in pharmaceutical formulations is as a solvent in the preparation of sustained-release intramuscular injections of steroids, such as estradiol valerate, hydroxy-progesterone caproate, testosterone enanthate, and nandrolone decanoate, or other oil-soluble drug substances, such as, the decanoates or enanthate esters of fluphenazine. The disappearance of sesame oil from the injection site, following subcutaneous or intramuscular administration to pigs, has been reported to have a half-life of about 23 days. ... 

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