PH, and drug absorption

Table 6 Influence of pH on Drug Absorption from the Stomach and Intestine of the Rata...

The importance of pH on drug absorption from the mouth has been extensively studied using the buccal absorption model, in which loss of drug from buffered drug solutions placed in the mouth is monitored. The influence of pH on the absorption of the weak base chloroquine and of the weak acid phenobarbitone is shown in Fig. 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

WN Charman, CJH Porter, S Mithani, JB Dressman. Physicochemical and physiological mechanisms for the effects of food on drug absorption the role of lipids and pH. J Pharm Sci 86 269-282, 1997. 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

The strategy of the preceding sections was based on predicting the permeabilities of drug compounds in the human jejunum. The rest of the intestinal tract has higher pH, and this needs to be factored in when considering models to predict not human permeabilities, but human absorption (see Fig. 2.3 and Table 7.2). 

Westman, J. Boulanger, Y. Ehrenberg, A. Smith, I. C. P., Charge and pH dependent drug binding to model membranes A 2H-NMR and light absorption study, Biochim. Biophys. Acta 685, 315-328 (1982). 

Although the pH-partition hypothesis and the absorption potential concept are useful indicators of oral drug absorption, physiologically based quantitative approaches need to be developed to estimate the fraction of dose absorbed in humans. We can reasonably assume that a direct measure of tissue permeability, either in situ or in vitro, will be more likely to yield successful predictions of drug absorption. Amidon et al. [30] developed a simplified film model to correlate the extent of absorption with membrane permeability. Sinko et al. [31] extended this approach by including the effect of solubility and proposed a macroscopic mass balance approach. That approach was then further extended to include facili-... 

In our own studies to establish an in-house correlation between Caco-2 permeability and extent of drug absorption in humans, a set of 25 model drugs was used (Table 5.1). The importance of concentration and pH conditions were investigated and transport was studied both in apical to basolateral (absorptive) and basolateral to apical (secretory) directions. The apparent permeability coefficients were determined at concentrations of 10, 50, and 500 pM, and at two different settings of apical/basolateral pH values 6.5/7.4 and 7.4/7.4. The marker compounds represented a good diversity in molecular structure and transport properties and covered a range of low (<20%), moderate (20-80%) and high (>80%) extent of absorption in humans (Tab. 5.1). 

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