Pharmaceuticals theophylline

X-ray powder diffractometry can be used to study solid state reactions, provided the powder pattern of the reactant is different from that of the reaction product. The anhydrous and hydrated states of many pharmaceutical compounds exhibit pronounced differences in their powder x-ray diffraction patterns. Such differences were demonstrated earlier in the case of fluprednisolone and carbamazepine. Based on such differences, the dehydration kinetics of theophylline monohydrate (CvHgN H20) and ampicillin trihydrate (Ci6H19N304S 3H2O) were studied [66]. On heating, theophylline monohydrate dehydrated to a crystalline anhydrous phase, while the ampicillin trihydrate formed an amorphous anhydrate. In case of theophylline, simultaneous quantification of both the monohydrate and the anhydrate was possible. It was concluded that the initial rate of this reaction was zero order. By carrying out the reaction at several... 

N-Mannich derivatization has also been documented to improve skin delivery [91][92], In the case of theophylline (11.56) and 5-fluorouracil (11.58), a much improved solubility in water of the various N-Mannich bases examined was observed. To avoid breakdown, however, the prodrugs had to be dissolved in a polar nonaqueous solvent (isopropyl myristate) for pharmaceutical use. The delivery of theophylline and 5-fluorouracil through hairless mouse skin was, thus, accelerated approximately sixfold through use of the prodrugs 11.57 and 11.59, respectively. 

A.M. Amado, M.M. Nolasco and P.J.A. Ribeiro-Claro, Probing pseudopolymorphic transitions in pharmaceutical solids using Raman spectroscopy Hydration and dehydration of theophylline, J. Pharm. Sci., 96, 1366-1379 (2007). 

In this section a variety of analytical separations reported in the literature are reviewed to show the wide structural diversity of eluite which can be separated by RPC and to assist the reader in becoming similar with the use of this fluid chromatographic technique. The descriptions are ar-ranged according to the matrix in which an analyte is found or the area of - h istry in which the samples are generally encountered. Thus theophylline, for example, is regarded as a nucleotide and, for the most part, its analysis in food samples is found with appropriate cross references. On the other hand, the separations of pharmaceuticals found in serum, urine, and pharmaceutical samples are cited separately. It is hoped that this method of classification may serve the purposes of those wh e analytical interests are incidental to their primary research pursuits. 

In addition to theophylline, purine or pyrimidine derivatives of pharmaceutical interest which have been analyzed include ftorafur, a fluorouracii derivative (429), arabinosides of adenine and hypoxanthine (408), ace-phylline (430), and allopurinol and oxipurinol (431). 

Fig. 3. Impact of development on theophylline plasma concentrations (from Ritschel WA and Kearns GL, 1999, reproduced by permission, from the Handbook of Basic Pharmacokinetics, 5th edn. 1999 by the American Pharmaceutical Association).

As a category of alkaloids with distinctive bioactivity, methylxanthine derivatives have in recent years received increasing attention in the food and pharmaceutical industries. The most important compounds of this class, characterized by a bitter flavor, are caffeine CF, theobromine TB, and theophylline TP (Fig. 6). 

Clements and Popli (1973) summarized transformation times during dissolution of pharmaceutical compounds from the literature. Theirstudy with meprobamate found that it took 168 h to convert to form I. Other than the example of chloramphenicol palmitate, this was much longer than most systems, which converted to the stable modiLcation in 300 s (theophylline) to 24 h (ampicillin). This is generally slow enough to allow therapeutic advantages to dosing the metastable solid orally, but too rapid to market suspensions of these forms with adequate physical stability. 

Renger, B., Jehle, H., Fischer, M., and Funk, W. Validation of analytical procedures in pharmaceutical analytical chemistry HPTLC assay of theophylline in an effervescent tablet. J Planar Chrom 8 269-278 (July/Aug. 1995). 

Natural products have served as a major source of drugs for centuries, and about half of the pharmaceuticals in use today are derived from natural products. Quinine, theophylline, penicillin G, morphine, paclitaxel, digoxin, vincristine, doxorubicin, cyclosporin, and vitamin A all share two important characteristics they are cornerstones of modem pharmaceutical care, and they are all natural products. The use of natural substances, particularly plants, to control diseases is a centuries-old practice that has led to the discovery of more than half of all modem pharmaceuticals. 

Contents 1. Introduction 373 2. Screening for and Preparation of Cocrystal Systems 375 3. Cocrystal Systems Having Pharmaceutical Interest 377 3.1. Cocrystal systems formed by carbamazepine- type molecules 378 3.2. Cocrystal systems formed by nicotinamide with carboxylic acids 380 3.3. Cocrystal systems formed by caffeine and theophylline 382 3.4. Cocrystal systems formed by saccharin 384 3.5. Cocrystal systems formed by carboxylic acids 385 References 386... 

I. Papadoyannis, M. Georgarakis, V. Samanidou, and G. The oridis, HPLC analysis of theophylline in the presence of caffe in blood serum qpd pharmaceutical formulations, J. Liquid Ch matogr., 74 1587 (1991). 

V. M. Shinde, N. M. Tendolkar, and B. S. Desai, Simultaneous determination of theophylline and etofylline in pharmaceutical dosages by HPTLC, Anal. Lett., 61 33 (1995). 

Typical probes for the analysis of ionic solutes include 3-hydroxy-L-tyrosine (DOPA)24 and naphthalene-2-sulfonate,26 whereas those for use with uncharged solutes include nicotinamide,27 theophylline,28 and anthracene 29 Indirect detection is nonspecific and less suitable for the analysis of complex or impure samples, because unpurified biological samples, such as urine, contain a large number of hydrophilic solutes that will give problems such as extra system peaks. However, analyses of pharmaceutical products and quantification of impurities in substances are typical of applications.23... 

Water dispersible microspheres containing 5-FU or theophylline units release pharmaceutically active molecules as well as water soluble ones. Figure 7 shows how hydroxyethyl-5-FU and hydroxyethyltheophylline release by ester hydrolysis of graft copolymers in aqueous dispersion solution by comparing that of the water soluble copolymers in homogeneous aqueous solution. As shown in the figure, the hydrolysis depends on the chemical structure of polymeric... 

Interactions between water vapor and amorphous pharmaceutical solids were evaluated using isothermal microcalorimetry. " The desorption of water from theophylline monohydrate has been investigated using microcalorimetric approaches.The properties of surfactants and surface-active drugs in solution were studied by Attwood et al. " using calorimetry, while titration microcalorimetry has been utilized to elucidate the nature of specific interactions in several pharmaceutical polymer-surfactants systems. " Drug decomposition was evaluated as a function of different... 

A pharmaceutical cocrystal is composed of an API and complementary molecules including excipients (non-toxic ingredients) or other APIs. Cocrystals may include two or more different components and in most cases to date, two and three component systems are reported with the latter being mostly cocrystalline solvates, e.g., theophylline 5-fluorouracil hydrate. Table 1 presents some examples of pharmaceutical cocrystals and solvates. The term cocrystal generally refers to components that in their pure states are solids at room temperature. It is important to note that a... 

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. ° ... 

Serajuddin, A.T.M. Jarowski, C.I. Effect of diffusion layer 54. pH and solubility on the dissolution rate of pharmaceutical acids and their sodium salts. II. Salicylic acid, theophylline and benzoic acid. J. Pharm. Sci. 1985, 74 (2), 148-154. 55. 

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