Tablet formulations dissolving

Sastry et al. [50] estimated primaquine in its tablet formulation. Powdered tablets equivalent to 100 mg of primaquine phosphate were dissolved in water, filtered, and filtrate was diluted to 100 mL with water. Portions of the solution were shaken with 3 mL of 5 mM brucine-0.16 M sulfuric acid, 1.5 mL of 5 mM sodium periodate and 2 mL of 1.2 M sulfuric acid and diluted to 9 mL with water. The solution was set aside for 20 min in a boiling water bath, cooled, and diluted to 10 mL with water. The absorbance was measured at 510 nm versus a reagent blank. Beer s law was obeyed from 20 to 140 pg/mL of primaquine phosphate. The coefficient of variation was 1.56% (n = 8). Recovery was 99.2%. 

The U. S. Dispensatory26 reports maximum serum levels of 0.2 ijg./ml. 1 hour after administration of a 250 mg. dose, 0.6 (ig./ml. 2 hours after a 500 mg. dose, and 1.2 ug./ml. 2 hours after a 1 g. dose. Higher blood levels are achieved on a multiple dosage schedule. Since it is acid labile, a resistant coating is used in tablet formulations to overcome the deleterious effect of gastric fluid on erythromycin base or the stearate salt is prepared which does not dissolve readily in the stomach. 

The source of the raw materials can greatly influence hydrolytic reactions. This is exemplified by Gold and Campbell [54] where talc obtained from different sources impacts markedly on the overall stability of the aspirin tablet formulation. This is possibly attributable to the effect of different types and amounts of surface impurities, which are dissolved in the adsorbed moisture layer, where they subsequently react with the API. It could also influence the pH of the micro-environment. 

TABLE 10.6 Dissolution Results, Reported as Percentage Drug Dissolved, for the 0.25 mg Target Tablet Formulation and Five Aberrant Tablet Formulations... 

DuraSolv is Cima s second-generation fast-dissolving/disintegrating tablet formulation and is also produced using direct compression but using higher compaction... 

Compressed tablet formulations contain different types of ingredients necessary for proper preparation and therapeutic performance. The ingredients needed include diluents, disintegrating or binding (adhesive) additives, and lubricants. Tablets are designed to be dissolved slowly in the mouth and should not disintegrate quickly. Lactose... 

Lozenges These are compressed tablets formulated, without a disintegrant and must be allowed to dissolve in the mouth. They are used for local activity (throat lozenges) or for systemic effect (vitamins). Effervescent tablets These tablets undergo quick dissolution of actives in water due to internal liberation of carbon dioxide. By combining alkali metal carbonates or bicarbonates with tartaric or citric acid, carbon dioxide is liberated when placed in water. 

Apart from immediate release tablet formulations, neural networks have also been applied to modeling immediate release capsule formulations and rapidly disintegrating or dissolving tablets. In the latter, Sunada and Bi from Japan used both statistics and neural networks to optimize both the formulation and processing conditions for rapidly disintegrating tablets developed using both direct compression and wet granulation techniques. 

Neural networks when applied to in vitro-in vivo correlations have the potential to be a useful predictive tool. Dowell et al. from the FDA and the Elan Corporation tested this hypothesis using a number of neural network architectures, on a data set including both in vitro inputs (% dissolved) and in vivo outputs (plasma concentrations). They concluded that the approach is viable—a conclusion also supported by studies by Chen et al. using a controlled release tablet formulation based on mixtures of hydrophilic polymers. 

Compare and contrast tablet formulation and gelatin capsule formulation. What might consequences be to the overall bioavailability of a drug if one formulation dissolves four times faster in the gut than another tablet formulation of the same drug ... 

USP XXII requires that not less than 70 % of the labelled amount of prednisolone is dissolved in 30 minutes in dissolution medium water (900 ml) with paddle stirring element test apparatus (apparatus 2) at 50 rpm (119). In vitro dissolution profiles of sustainecj release formulations of prednisolone are given. For each tablet formulation 20 tablets were placed in a 100 ml beaker of 5.5 cm diameter 35 ml of distilled water were added and the contents were stirred for one hour, at 37°C. Sustained-release formulation gives a more uniform blood level of prednisolone and avoids high peaks of plasma prednisolone (120). 

Heptakis (2,6-di-0-methyl)-fi-cyclodextrin (DMCD). Solinis et al. [60] used hydrophilic DMCD along with HPMC (in six of nine tablet formulations), with the presumption that the aromatic ring of the drug could increase the possibility of stereoseleetive interaetion between salbutamol enantiomers and DMCD. However, stereoseleetive release or interaetion was not observed. In the capillary electrophoresis, in whieh DMCD was added to the buffer, resolution of the enantiomers was noted. In these formulations, cyclodextrins tend to dissolve quickly or disintegrate the matrix too fast to allow for diffusion or enantioselective drug release to take place. 

Information is very limited, but the interaction seems to be established. It is not likely to occur with solid form, fast-dissolving digoxin preparations (e.g. liquid-filled capsules) or digoxin in liquid form, but only with those preparations which are slowly dissolving (i.e. some tablet formulations). A reduction in digoxin levels of one-third could result in under-digitalisation. There seems to be no information about digitoxin. 

Another study by the same workers showed that propantheline increased the digoxin serum levels of a slow-dissolving tablet formulation Orion) by 40%, but had no effect on serum digoxin levels with a fast-dissolving tablet formulation Lanoxin) In a further study, propantheline increased the AUC of digoxin from Lanoxin tablets by 24%, compared with a non-significant increase of 13% with digoxin in the form of a solution in a capsule Lanoxicaps) ... 

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