Aggregation of antihistamines in aqueous solution: effect of counterions on self-association of pyridine derivatives.

The effects of electrolytes on the self-association of the antihistaminic drugs, tripelennamine hydrochloride, thenyldiamine hydrochloride, pyrilamine maleate, pheniramine maleate, chlorpheniramine maleate, and brompheniramine maleate, in aqueous solution were examined by light-scattering from tripelennamine bydrochloride and thenyldiamine hydrochloride in 0.154 mole of sodium chloride/kg and 0.150 mole of sodium maleate/kg indicated a micellar pattern of aggregation. Higher aggregation numbers and lower CMC's were determined in the presence of the maleate ion. No significant discontinuity in the concentration dependence of the light scattering of the remaining compounds in either of the two electrolytes was evident, and the aggregation of these compounds was treated using a stepwise association model. Values of the association constants and the limiting number of associating species were, in general, increased by the addition of electrolyte in the order water less than sodium chloride less than sodium maleate. An apparently nonmicellar pattern of aggregation could be induced by chemically changing the counterion from chloride to maleate.

The interaction of antihistamines with lecithin monolayers.

The interaction of a series of antihistamines with monolayers of L-alpha-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6-8. It was not clear whether this effect was caused by the buffer components or was a pH effect.

Aggregation of antihistamines in aqueous solution. The effect of electrolyte on the miscellar properties of some diphenylmethane derivatives.

The effect of sodium chloride on the micellar properties of the antihistamines, dephenhydramine hydrochloride, bromodiphenhydramine hydrochloride, chlorcyclizine hydrochloride and diphenylpyraline hydrochloride in aqueous solution has been investigated by light scattering and viscometric methods. The drugs behaved as typical ionic surfactants showing an increase in aggregation number and decrease in critical micelle concentration as the electrolyte concentration was increased over the range 0.05 to 0.154 mol kg-minus1. A linear relation between log critical micelle concentration and log counterion concentration was established, from which values of the degree of ionization and the free energy of micellization were calculated. The intrinsic viscosity was decreased by the addition of electrolyte and this has been attributed to a decrease in micellar hydration due to a removal of hydrogen-bonded water.

The surface activity of some antihistamines at the air-solution interface.

The surface activity of some antihistamines at the air-solution interface has been examined. Change of the counterion associated with the drug from chloride to maleate or chloro-theophyllinate considerably decreased the critical micelle concentration and increased the surface activity. The effect on surface activity of changes in the nature of the hydrophobic and hydrophilic groups have also been evaluated.

Some emulsifying and suspending properties of a polysaccharide gum derived from Mucuna flagillepes, Papilionaceae.

The emulsifying and suspending properties of a new polysaccharide gum derived from an edible bean, Mucuna flagillepes have been investigated. The stability of the emulsion prepared with the gum was compared with that of emulsions prepared with acacia or tragacanth. Sherman's equations for concentrated emulsions were applied to determine the rate of coalescence k, and changes in mean cube globule diameter. Suspensions of sulphdimidine or zinc oxide prepared with tragacanth gum were compared with those prepared with mucuna gum. The final sedimentation height, Hu for each suspension was predicted using a biexponential relationship in the sedimentation pattern. The indication is that mucuna gum can be usefully employed as both an emulsifying and a suspending agent.

Preliminary evaluation of dika fat, a new tablet lubricant.

Dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonensis var excelsia has been evaluated as a lubricant on the basis of its effect on the flow rate of granules, disintegration time and dissolution rate of tablets. The fat shows a maximal effect on flow at a concentration of 2.5% w/w. It produces better disintegration and dissolution profiles than magnesium stearte at all concentrations tested. The indication is that there is less degradation of aspirin in tablets containing this oil than there is in tablets containing magnesium stearate. The use of Dika fat (m.p. 39--40 degrees C) eliminates the hydrogenation step often necessary for vegetable oils.

Comparative evaluation of two direct compression lactose grades for pyridoxine hydrochloride tablets.

Fast flow lactose (FFL) and anhydrous lactose (AHL) were comparatively investigated for the manufacture of pyridoxine hydrochloride tablets. The results showed that drug/FFL formulations possessed better performance. Harder tablets were, however, compressed from AHL blends. Linear relationships which correlate tablet physical properties to excipient concentration in a given formulation were established. Tablet batches formulated with FFL dissolved in shorter times und showed better stability characteristics on aging.

Binding effectiveness of Colocassia esculenta gum in poorly compressible drugs-paracetamol and metronidazole tablet formulations.

The effectiveness of a polysaccharide gum obtained from the cormels of Colocassia esculenta was evaluated comparatively with acacia and methylcellulose as binders in the formulation of poorly compressible drugs. The granules of these drugs produced by wet massing method using colocassia and acacia gums as binders have high compressibility index indicating poor flow. Based on this parameter, the granules produced with methylcellulose as binder seem to flow better. The properties of tablets evaluated include breaking strength, friability, disintegration time and dissolution rate. The new polysaccharide gum showed better concentration-strength profile than acacia while methylcellulose yielded mechanically more stable tablets than the two binders. The resistance of tablets to abrasion was poor in metronidazole tablets formulated with colocassia gum. The in vitro availability characteristics showed that tablets produced with the new gum show acceptable disintegration time and release profile within a certain range of its concentration in tablets. At 4% w/w nominal concentration of colocassia gum in metronidazole tablets and 6% w/w in paracetamol, tablets show very long disintegration time and prolonged release profile. The binders used for comparison yielded tablets that show better in vitro release characteristics.

Cissus stem gum as potential dispersant in pharmaceutical liquid systems 2: The emulsifying and suspending properties.

The emulsifying and suspending properties of a new gum derived from the stem of cissus rufescence family Amphelidaceae were studied. Stability of the liquid paraffin emulsions prepared using this mucilaginous substance was compared with that containing tragacanth or acacia. The rate of globule coalescence was determined using Sherman's equation for concentrated emulsions. The suspending ability of the polymer was compared with that of tragacanth or compound tragacanth. The rate of deflocculation, K, was found to obey a power law equation: beta t = beta 0 e-kt in zinc oxide suspensions. At concentrations above 0.75% w/v, cissus gum produced liquid paraffin emulsion with minimal separation. The rate of globule coalescence was in the order acacia > cissus > tragacanth and rate of creaming was tragacanth > acacia > cissus. At concentrations of 0.6 to 1.0% w/v, cissus gum produced highly flocculated zinc oxide suspensions, which exhibited good redispersibility. Stability of the agglomerated, dispersed particles was similar to that produced using tagacanth mucilage.

Cissus stem gum as potential dispersant in pharmaceutical liquid systems: rheological characterization.

A Co-axial viscometer, the Haake-Rotovisco, was used studying the rheological behaviour of aqueous dispersion of cissus stem gum. At concentrations of 4% w/v and above, the mucilage is both pseudoplastic and thixotropic. Two equations derived from a power law expression for apparent viscosity(h): h = ekc + b were solved simultaneously (c = 4 and 8% w/v) in the determination of material constants k and b for cissus gum. The apparent viscosity of the polymeric liquid system was affected by concentration of the gum, pH, temperature and aging.

A comparative study of modified starches in direct compression of a water soluble drug-chloroquine phosphate.

Some in vitro properties of chloroquine phosphate tablets formulated with four modified starches were investigated. The drug was formulated as tablets containing 250 mg of chloroquine phosphate and produced by the direct compression technique. The starches were isolated from maize, zea mays, rice, Oryza sativa, cassava, Manihot esculenta and cocoyam, Zanthosoma sagittifolium. They were modified through physicochemical process, Sta-Rx 1500, a directly compressible starch was used as basis for comparison. The hardness of the chloroquine tablets generally decreased to a minimum with all the modified starches at concentration level of 40% and with maximum hardness obtained when their concentrations were increased to 80%. The least hardness values were obtained with modified cocoa yam starch while the highest hardness values were obtained with modified rice starch. Modified rice and cassava starches produced chloroquine tablets that exhibited higher mechanical properties than those of modified maize starch, cocoayam starch and Sta-Rx 1500. On the basis of dissolution profile of chloroquine phosphate tablets, the modified starch samples were ranked in order of increasing dissolution as modified cocoayam maize Sta-Rx 1500 cassava rice starch sample. The release rate of chloroquine was found to be dependent on the physico-chemical properties of the individual modified starch granules such as particle size and degree of gelatinization.

A comparative study of modified starches in direct compression of a poorly water soluble drug (hydrochlorothiazide).

The direct compression properties of four modified starches in hydrochlorothiazide (HCTZ) tablets were studied. The starches were obtained locally from common plant sources and were modified through physicochemical treatment. Each modified starch was used as the only filler-binder-disintegrant in the formulation of hydrochlorothiazide tablets containing 25 mg of the drug. The tablets were produced by the direct compression technology. Sta-Rx 1500, a directly compressible starch, was used as basis for comparison. Evaluated tablet properties included weight and drug content uniformity, hardness and friability as well as disintegration time and dissolution profile. The modified starches exhibited species specificity in terms of the tablet properties. The weight, drug content and disintegration time for all batches of tablets were within acceptable limits. Proper ranking of the starches on the basis of specific tablet properties was used to highlight their differences.