Formulation of medicines

The industry knows that it has to learn to live with restrictions of some kinds and one of the means of restriction is the formulary, a list of formulations of medicines with varying amounts of added information. A formulary may list all nationally licensed medicines prescribable by health professionals, or list only preferred drugs. 

Nunn T, Williams J. Formulation of medicines for children. Br J Clin Pharmacol 2005 59 674-676. 

Schirm E, Tobi H, De Vries TW (2003) Lack of appropriate formulations of medicines for children in the community. Acta Paediatr 92(12) 1486-9... 

Spans and Tweens have been used to overcome similar problems in the formulation of medicines for internal use. The solubilization of resinous components of tinctures such as benzoin and myrrh in aqueous vehicles and the incorporation of water-soluble ingredients into oily vehicles has been discussed by Stoklosa and Ohmart [230]. Gerding and Sperandio [229] give examples of mixtures of tinctures and fluid extracts which, on addition of polysorbate 20, will not precipitate on dilution. Cetomacrogol 1000 added in small amounts to opiate linctus of squill, syrup of ginger, compound mixtures of camphor, and of lobelia and stramonium has a similar clearing action [207]. 

Micellar solubilization occurs over a relatively small surfactant concentration range because of this and because the phenomenon is never observed in isolation, we have extended the text to include surface activity, emulsions and suspensions and, as our emphasis is on formulation of medicinal products, to the difficult topic of the toxicology of surface-active agents. It is clearly not possible to produce a text which reviews all of these areas in great detail what we have attempted to do is to deal with those aspects of the subject matter which are relevant in the formulation and use of surfactants in pharmacy and in formulation of products for human and animal use. The consequences of the inclusion of surfactants into such formulations is considered in some detail. The held is widened to include discussion of related problems of the use of surfactant formulations in agriculture and horticulture. Since 1968 there has been an increased awareness of the potential and limitations of surfactant systems. 

Preservative availability may be appreciably reduced by interaction with packaging materials. Examples include the permeation of phenolic preservatives into the rubber wads and teats of multi-dose injection or eye-drop containers and by their interaction with flexible nylon tubes for creams. Quaternary ammonium preservative levels in formulations have been significantly reduced by adsorption onto the surfaces of plastic and glass containers. Volatile preservatives such as chloroform are so readily lost by the routine opening and closing of containers that their usefulness is somewhat restricted to preservation of medicines in sealed, impervious containers during storage, with quite short use lives once opened. 

Brigitte Mars, an herbalist and nutritional consultant in Boulder, Colorado, has been working with natural medicines for over 27 years. The formulator of the popular "UniTea" line of herbal teas, she teaches herbalism at Naropa Institute, The Rocky Mountain Center for Botanical Studies and The Boulder School of Massage Therapy. She frequently contributes articles to The Herb Companion, Natural Health, Let s Live, and other magazines, and is a member of the American Herbalist Guild. This is her first book. 

The formulation of timed-release medicines is based on the specific response of polymeric coatings to their chemical environment. The chemical packaging of these medicines determines the precise conditions for effective control and sustained dosage of these drugs. 

Widespread medicinal use of colloidal bismuth subcitrate (CBS) has prompted extensive studies of bismuth compounds involving the citrate anion. Bismuth citrate is essentially insoluble in water, but a dramatic increase in solubility with increasing pH has been exploited as a bio-ready source of soluble bismuth, a material referred to as CBS. Formulation of these solutions is complicated by the variability of the bismuth anion stoichiometry, the presence of potassium and/ or ammonium cations, the susceptibility of bismuth to oxygenation to Bi=0, and the incorporation of water in isolated solids. Consequently, a variety of formulas are classified in the literature as CBS. Solids isolated from various, often ill-defined combinations of bismuth citrate, citric acid, potassium hydroxide, or ammonium hydroxide have been assigned formulas on the basis of elemental analysis data or by determination of water and ammonia content, but are of low significance in the absence of complementary data other than thermal analysis (163), infrared spectroscopy (163), or NMR spectroscopy (164). In this context, the Merck index lists the chemical formula of CBS as KgfNHJaBieOafOHMCeHsCbh in the 11th edition (165), but in the most recent edition provides a less precise name, tripotassium dicitrato bismuthate (166). 

Combinations of active ingredients, specific pharmaceutical formulations, specific use, and company names can be included in the product name. Examples of this are shown in Table 8.2. This combinations and mixes of names can be very complicated and disturbing for the health-care and for the patients, especially for the elderly. It not easy to know what is important. Is ZOC a company or a pharmaceutical formulation changing the dosing schedule Patient safety in the reconciliation of medicines as described in Chapter 10 is very important and must not be neglected. 

All stages involving the evaluation and formulation of a new medicine (after the medicine has been discovered and has gone through preclinical testing), until it reaches the market. 

Mann, C. and Staba, E.J., 1986, The Chemistry, Pharmacology, and Commereial Formulations of Chamomile. In Herbs, Spices, and Medicinal Plants Recent Advances in Botany, Horticulture, andPharmocology (L. E. Craker, and J. E. Simon, eds.). Oryx, Phoenix, AZ, Vol. 1, pp 235-280. 

Gareth Kilian completed his undergraduate B.Pharm. degree at the University of Port Elizabeth in 1999. In 2002 he completed his M.Sc. degree in medicinal chemistry Cum Laude, also at the University of Port Elizabeth, were his work was directed on the medicinal chemistry of aromatic cyclic dipeptides. He has since worked as a community service pharmacist in 2002 at Butterworth Hospital in the Eastern Cape, after which he was employed as a lecturer in Pharmaceutics at the NMMU, where he currently works. He is a Ph.D. candidate at the NMMU under Professor Pieter Milne, also working on cyclic dipeptides. He has coauthored several peer-reviewed manuscripts in international journals as well as supervising and cosupervising a number of M.Sc. candidates over the past 6 years in the fields of medicinal chemistry and pharmaceutical formulation. 

Supply on a particular patient basis encompasses various categories of unauthorised use of medicinal products. A product maybe imauthor-ised because it has been specially formulated for use it may be at the clinical trial stage of development, but be requested by doctors for use outside a trial it may have been authorised previously and then withdrawn from the market for commercial reasons, or because of safety, efficacy or quality concerns or it may be authorised currently, but for a different indication or patient population, or in a different country. 

By the time that an application for a product licence is ready, a certain amount of evidence on the safety of the drug will be available. In a review of product licence applications to the Committee on Safety of Medicines (CSMs), Rawlins and Jefferys presented data on the number of patients who were available for the assessment of safety and efficacy (Table 15.5). When it is considered that many of the patients included would have been in short-term clinical trials (up to 28 days), and that other trials would have been conducted on formulations and doses that were different from those recommended in the product licence application, then the relevant numbers are substantially reduced. 

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