Formulations topical

Topical Formulations. Topical formulations by their very nature are usually multicomponent, and it is not surprising that neural networks have been applied to deal with this complexity. The first work was performed on hydrogel formulations containing anti-inflammatory drugs in Japan in 1997 [57], followed up by further studies in 1999 [58] and in 2001 [59]. Lipophilic semisolid emulsion systems have been studied in Slovenia [60, 61] and transdermal delivery formulations of melatonin in Florida [62]. In all cases, the superiority of neural networks over conventional statistics has been reported. 

Rifaximin is broad-spectrum antibiotic, which covers many skin pathogens, whose lack of transcutaneous absorption has been well documented by both animal [8] and human [9] studies. On these grounds, a topical formulation (i.e. cream) containing 5% of the active compound was developed and tested in the treatment of pyogenic skin infections. Some open trials [20, 21] showed the efficacy and safety of the formulation and pointed out the lack of selection of resistant strains after topical application of rifaximin. In any event, drug delivery from the topical formulation is orders of magnitude higher than the... 

Strongly basic antibiotics may be precipitated by formation of the coloured reineckate salt which may then be determined spectrophotometri-cally 65. Bickfordl66 dissolved the precipitated neomycin reineckate in acetone and has successfully used this procedure to assay neomycin extracted from topical formulations. Roushdi et al 73 preferred to oxidise the precipitate with potassium permanganate and then colorimetrically estimate the chromate produced with diphenylcarbazide. 

Buffers are compounds or mixtures of compounds that, when present in solution, resist changes in pH upon the addition of small amounts of acids or alkali. In essence, they are capable of maintaining the pH values relatively constant and, therefore, are insensitive towards addition of small quantities of acids and/or bases. The ability to resist changes in pH is called buffer action. Buffers are added to topical formulations to control the pH that provides an acceptable balance between chemical stability, therapeutic activity, and comfort. 

C. B. Lalor, G. L. Flynn, and N. Weiner. Formulation factors affecting release of drug from topical formulations. I. Effect of emulsion type upon in vitro delivery of ethyl p-aminobenzoate. J. Pharm. Sci. 83 1525-1528 (1994). 

Little is known on the metabolic fate of l-methylpyrrolidin-2-one (5.60), an industrial solvent also useful as a solubilizing agent and a penetration enhancer in topical formulations. A preliminary investigation of the disposition and metabolism of labeled l-methylpyrrolidin-2-one in the rat showed that the compound is excreted mainly in urine [171]. Three urinary metabolites were detected, the major of which (ca. 15% of the dose) was 4-(methylami-no)but-2-enoic acid (5.61). This unsaturated product may likely have been formed by H20 elimination from a hydroxylated metabolite. 

Topical formulations are another special case. Over time, it has been shown that the minipig has a skin structure that is quite similar to humans, and that species is now used commonly as the nonrodent model. These types of formulations also require local irritation studies where guinea pigs are used to determine delayed contact sensitization. Selection of the animal species for the nonclinical program is often not straightforward. 

Composition (E), (Figure 1, R=Ci2H25) had many of the sought-after attributes however, border line saline compatibility in topical formulations was viewed as a weak point. By contrast, composition (F) had the same desirable features with the added advantage of saline compatibility in formulated products. Therefore, composition (F) became a leading candidate for topical contraceptive development. 

Shah, V. R, Progress in methodologies for evaluating bioequivalence of topical formulations. Am. J. Clin. Dermatol., 2, 275-80, 2001. 

Recently, Loden et al. [83] investigated the use of titanium dioxide as an opaci-fier in topical formulations of ketoprofen. The results demonstrated qualitative differences in the level of photostabilisation based on the grade of titanium dioxide utilised. Surface-coated particles were shown to induce greater photostabilisation than pharmaceutical grades of the excipient. The authors showed clear superiority of the opacified topical formulation containing 4% titanium dioxide versus the standard clear gel. 

Pharmacokinetics The transdermal absorption of tretinoin from various topical formulations ranged from 1 % to 31 % of applied dose, depending on whether it was applied to healthy skin or dermatitic skin. 

Topical formulations of nystatin and of amphotericin B are useful in the management of Candida albicans infections of the skin. Both antibiotics are ineffective against dermatophytes. The use of nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and its negligible absorption from the gastrointestinal tract. Hypersensitivity reactions are rare. It is not known whether topical nystatin can cause fetal harm when used by a pregnant woman. Amphotericin B has broader antifungal activity but its topical use is restricted to Candida. Topical use of amphotericin B has shown minimal absorption through the skin and is well tolerated. Limited human surveillance data do not indicate any harm to mother or fetus, but relative safety is still unknown. 

Korting HC, Kiencke P, Nelles S, Rychlik R. Comparable efficacy and safety of various topical formulations of terbinaflne in tinea pedis irrespective of the treatment regimen results of a meta-analysis. Am J Clin Dermatol 2007 8(6) 357-64. 

Ketorolac (Toradol), an NSAID chemically related to indomethacin and tolmetin, is mainly used as an analgesic, not for the treatment of inflammatory disease. It is available in oral, parenteral, and topical formulations. 

Bexarotene is available in oral and topical formulations. Peak plasma levels are achieved within 2 hours of oral administration, although higher levels are obtained when the drug is ingested with a fatty meal. It is thought to be metabolized primarily by the hepatobiliary system, with a terminal half-life of approximately 7 hours. 

Penciclovir is approved as a topical formulation for the treatment of herpes labialis. In immunocompetent individuals, penciclovir shortens the duration of lesion presence and pain by approximately half a day when it is initiated within an hour of lesion development and applied every 2 hours during waking hours for 4 days. 

Currently, production of eflornithine has been stopped because of industrial policy and environmental problems it involves the use of Ereon (CHF2CI) as a reagent in its synthesis (Eigure 8.27). However, production of eflornithine may start again in order to supply the WHO. Another reason is that a topical formulation for the treatment of female hirsutism has recently been launched (Vaniqa). Its synthesis has recently been improved by using the selective catalytic reduction of the cyano group without any cyclization into lactam. ... 

This book is a companion volume to Pharmaceutical Technology Controlled Drug Release, Volume 1, edited by M.H.Rubinstein and published in 1987. It focused on the different types of polymeric materials used in controlled release. This book extends these concepts to include drug properties, design and optimization, coating, the effect of food and pharmacokinetics. It also reflects the growing interest in biodegradable polymers in oral and topical formulations and the use of sterile implants. 

The bioavailability of oral acyclovir is low (15-20%) and is unaffected by food. An intravenous formulation is available. Topical formulations produce high concentrations in herpetic lesions, but systemic concentrations are undetectable by this route. 

Neomycin is available in numerous topical formulations, both alone and in combination with polymyxin, bacitracin, and other antibiotics. It is also available as a sterile powder for topical use. Gentamicin is available as an ointment or cream. 

Alitretinoin (Panretin) is a topical formulation of 9-c/s-retinoic acid which is approved for the treatment of cutaneous lesions in patients with AIDS-related Kaposi s sarcoma. Localized reactions may include intense erythema, edema, and vesiculation necessitating discontinuation of therapy. Patients who are applying alitretinoin should not concurrently use... 

Table 61-3 lists topical formulations for the treatment of seborrheic dermatitis. These are of variable efficacy and may necessitate concomitant treatment with topical corticosteroids for severe cases. 

Ueno, H., Mori, T., and Fujinaga, T. (2001). Topical formulations and wound healing applications of chitosan. Adv. Drug Deliv. Rev. 52,105-115. 

Based on the results from these three trials, BioCryst has initiated a multicenter Phase III trial for the treatment of CTCL, as well as a large, multicenter Phase II trial for psoriasis. In addition to the two clinical trials using the topical formulation, a Phase I clinical trial in CTCL and T-cell lymphoma/leukemia has begun using an oral formulation of BCX-34. In the future, a number of other T-cell mediated diseases or processes are possible targets for BCX-34, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and organ transplant rejection. 

The use of excipients goes back to centuries. Even before the advent of the capsule and later the tablet, the available botanical drugs were made into powders or mixtures to make them more convenient for the patient, although sometimes not that palatable. Ointments and salves, with similarities to topical formulations that have been used in more recent times, were known in Ancient Greece. However, the scientific basis for the use of certain excipients has emerged only in the last few decades for example, tablet lubricants—until a few years ago we knew they were needed and when to use them, but not why they functioned as they do. 

Certain APIs are administered topically, e.g., topical anti-inflammatory steroids and topical anti-fungal agents. The release of these APIs from their formulation was thought to be maximized when the solution of the drug in the vehicle is just saturated (27). However, Davis and Hadgraft (28) have shown that supersaturation can increase the penetration even further. The interaction of the moisture present in the skin with the topical formulation can be used to change the degree of saturation of the formulation and thereby enhance the release of the API from the formulation into the skin. 

Rafiee-Tehrani M, Mehramizi A. In vitro release studies of piroxicam from oil-in-water creams and hydroalcoholic gel topical formulations. Drug Dev Ind Pharm 2000 26(4) 409-414. 

The guidance specifies the application information that should be provided to the Center for Drug Evaluation and Research (CDER) to ensure continuing product quality and performance chacteristics of the sernisolid topical formulation for specified changes. The guidance does not comment on or otherwise affect compliance/inspection documentation defined by the Office of Compliance in CDER or the Office of Regulatory Affairs at FDA. 

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