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Granisetron, Ondansetron and Tropisetron, three 5-HT3 antagonists showing anti-emetic activity, were analysed by HPLC on lipophilic stationary phases. The addition of an amine or quaternary ammonium salt to the eluents was a powerful tool in the analysis of these basic substances. The influence on chromatographic parameters of pH, ionic strength and various counter-ions in the aqueous phase as well as of different organic modifiers is discussed. Some of the proposed experimental conditions allow a more strictly partition-based separation mechanism and can produce chromatographic parameters suitable for structure-activity studies. These experimental conditions are also suitable for analysis of the considered compounds in pharmaceutical dosage forms or in biological fluids.

Matrix properties and release behaviour of monolithic devices based on a water soluble polymer has been investigated. Polyethyleneoxides of different molecular weights have been used and different molecular weight fractions have been blended in order to tune the release mechanism. Drug release kinetics have been closely related to swelling and dissolution properties of the adopted matrices. In particular the development of the external swollen layer of the tablet as well as the kinetic of dissolution have been monitored. The different drug delivery behaviours observed were related to the different matrix properties. Viscoelastic properties of the matrices have been also investigated. In fact, in order to obtain effective bioadhesive drug release devices, apart from the intrinsic mucoadhesive capabilities of the used polymers, also the viscoelastic properties of the water-polymer gel must also be taken into account. A good interpenetration between the adjacent layers of the mucus and the polymer gel is ineffective in holding the mucoadhesive tablet at a specific site if the polymer gel does not have a proper viscoelastic behaviour. The best compromise between good release, viscoelatic and mucoadhesive properties was obtained in the case of 50\% by weight blend of the two adopted polymer fractions (600,000 and 4,000,000 molecular weight).

Forty-​six 1- or 2-​substituted benzotriazole derivs. were tested for their auxin-​like activity by the oat coleoptile elongation test and for their herbicidal activity as a function of their structure and of concn. At low and medium concns., these compds. behave as growth stimulators, while at highest concns. they are growth inhibitors. At concns. from 10-​6 to 10-​9 M, most of these compds. are more active than IAA. The presence of a functional group at C-​1 leads to an increase of activity. A few of these compds. showed a weak herbicidal activity on Yellow foxtail in a soil test, whereas practically no activity was obsd. with this plant in the foliar application. None of these compds. behaved like 2,​4-​D. Soil-​applied 2-​(benzotriazol-​2'-​yl)​propionamide was active (herbicide) on a no. of tested plants, but was inactive when applied foliarly.

On the basis of a previous equation correlating structural features and auxin-​like activity, new sets of benzotriazole derivs. bearing in the position 1 or 2 a cycloalkyl residue, or substituents such as -​CH(CH3)​(CH2)​n-​COR', -​CH(COR')​(CH2)​n-​CH3, and -​C(CH3)​2 COR' (R' = OH, OEt; NH2) were prepd. and tested. An overall correlative equation which accommodates all the 106 benzotriazole derivs. was developed. Evidently, the bulkiness rather than asym. of the carbon attached to the heteroring nitrogen was responsible for extra activity. Moreover, structural features such as branching and -​COR' group play an additive role only when the component parts of the N-​substituent are properly structured.

A thorough investigation on the dependence of octanol/water distribution coefficients (log D) of basic and amphiprotic beta-blocker drugs on pH and pKa values has been carried out. An attempt is made to clarify the factors which govern the chromatographic parameters (log k') in reversed-phase high performance liquid chromatography (RPLC) in terms of chemical structure and of distribution coefficients. The correlations between log D and log k' of different compounds show that the bulkiness and the branching of nitrogen substituent are controlling factors in RPLC measurements. Finally, an ion pair chromatographic system is considered for the prediction of octanol/water partition coefficients.

A simple approach is presented to modulate drug delivery from swellable systems by using complexants. The effect of complexants has been interpreted by means of simple mass balances on diffusing species and the involved relevant parameters have been individuated. The application of this strategy to the release of nicardipine (NIC) from swellable systems by using beta-cyclodextrin (CD) as complexant has evidenced the potential of the approach to tailor drug release. Crosslinked polyethyleneglycol has been synthesized, characterized and used as the swellable matrix. Swelling kinetics, NIC and CD diffusivities in the swollen matrix and NIC/CD phase solubility studies have been performed. The polymer matrix has been loaded with pure NIC or with NIC and CD at different ratios and release kinetics evaluated. Release profiles have shown that the presence of CD significantly affected drug delivery by decreasing the effective diffusivity of NIC. The higher the CD/NIC ratio the slower is the release. This effect has been interpreted on the basis of the proposed model and physically sound assumptions.

A thorough investigation on the dependence of distribution coefficients of acidic drugs on pH and pKa values has been carried out. The results give evidence that the Henderson‐Hasselbach equation is an idealization and only an approximation for real systems. It is shown that a multiparametric curve‐fitting technique may constitute a useful alternative to the previously reported methods to describe the hydrophilic/lipophilic pH‐profiles of ionogenic substances. Calculated values at any given pH value are in very good agreement with the experimental partition (log P) and distribution coefficients determined by shake‐flask method and reversed‐phase high performance liquid chromatography. Copyright © 1986 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim