Pharmaceutical Technology: Controlled Drug Release, Volume 2

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CH. 2] THE EFFECT OF ELECTROLYTES AND DRUGS 25 Table 1—The effect of pH on the cloud point of 2% K100 gels RESULTS AND DISCUSSION Effect of pH on cloud points. Although HPMC is not thought itself to be pH sensitive [6], the pH of a dissolution fluid is known to affect release rates of drugs from its matrices via the suppression of ionization [7]. The cloud points at 2% K100 gels (Table 1) were only affected by pH at low pHs. It was therefore considered unnecessary to modify the pH of electrolyte solutions used to determine cloud points. The effect of inorganic salts and drugs on the cloud point of 2% HPMC gels Fig. 1 gives typical data. As the ionic strength of a particular electrolyte increased, the cloud point deceased (Tables 2 and 3). The ability of an electrolyte to salt out a polymer from its solution generally followed the salts’ order in the lyotropic series. The relation between cloud point reduction and concentration of salt is generally thought to be linear but the relation is probably more complicated. At the low concentration of 0.02 M both drugs and electrolytes generally lowered the cloud point but at higher concentrations the drugs tended to raise the cloud point while the salts lowered it. The cloud point may be regarded as a limit of solubility, since the turbidity produced is due to HPMC precipitating from solution. Equation (2) was used to determine the effect of salt concentration on the cloud point. Thus, where log CP is the observed cloud point of HPMC in the solution of the electrolyte, log CP 0 is a theoretical cloud point based on the intercept at zero solute concentration, K CP is a salting-out constant analogous to that in equation (2) and m is the molal concentration. The gradient of the straight line, K CP , is positive for ‘salting in’ and negative for ‘salting out’. Values calculated by linear regression are given in Tables 2 and 3 respectively. It can be seen that the various sodium phosphate salts rank as tetrasodium pyrophosphate>trisodium orthophosphate>disodium hydrogen ortho-phosphate>sodium dihydrogen orthophosphate in order of their salting-out ability. The decrease in cloud point increased as the valence of the phosphate ion increased. However, in terms (2)
26 MATRIX FORMULATIONS [CH. 2 Fig. 1—The effect of temperature on the light transmission of 2% HPMC K15M gels in water containing Na 2 HPO 4 . of ionic strength, sodium dihydrogen orthophosphate, the univalent salt, gave the greatest reduction. Additionally, the sodium salts more readily caused salting out than their corresponding potassium salts. The anions played a more significant role in determining cloud point reduction than cations; cf. Al 3+ and Na + . The cloud points involving HPMC K15M gels were lower than those of HPMC K100 gels, a difference of ~2°C being noted. Sarkar [4] found ~6°C differences between the cloud points of 2% HPMC K100 and 2% HPMC K4M gels. Touitou and Donbrow [8] noted that large ions, e.g. tetracaine hydrochloride, sodium salicylate and sodium benzoate, each with low affinities for water, raised the gelation temperature of HPMC. The effect is explained on the basis that a large ion is adsorbed onto the macromolecule, carrying with it water molecules raising the degree of hydration of the colloid. Quinine bisulphate, in spite of being water soluble and containing sulphate ions, did not affect the cloud point. One explanation could be that the hydrating effect of the quinine molecule was counteracted by the dehydrating effect of the sulphate ion (Table 2). The poorly water-soluble theophylline did not affect the cloud point. Aminophylline and tetracycline hydrochloride gave straight line relationships between their concentration in gels and the observed cloud points. In the case of tetracycline this did not explain a non-Higuchian release pattern previously found during dissolution from tetracyline-HPMC matrix tablets which was thought to be caused by a complex drug-HPMC gel interaction [3].
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CH. 6] CONTROLLED RELEASE MATRIX TA
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7 A new ibuprofen pulsed release or
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CH. 7] A NEW IBUPROFEN PULSED RELEA
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108 MULTIPARTICULATES [CH. 9 Fig. 2
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118 CH. 10] CONTROLLED DELIVERY OF
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126 CH. 11] THE EFFECT OF FOOD ON G
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128 CH. 11] THE EFFECT OF FOOD ON G
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132 CH. 12] BIODEGRADABLE POLYMERS
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142 CH. 13] A COMPARISON OF DISSOLU
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156 OPHTHALMIC FORMULATION [CH. 14
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162 CH. 15] A SUSTAINED RELEASE OPH
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172 IMPLANTS [CH. 16 The purpose of
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174 IMPLANTS [CH. 16 times with 5 m
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176 IMPLANTS [CH. 16 noted that the
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178 IMPLANTS [CH. 16 Fig. 1—The e
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180 IMPLANTS [CH. 16 Table 3—Tobr
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184 CH. 17] SILICON MATRIX SYSTEMS
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194 INDEX dry granulation, 43 elect
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Pharmaceutical Technology: Controlled Drug Release, Volume 2

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