Tablet drug release prevention

Drug release profiles from the tablets in various dissolution media are shown in Fig. 2. In all cases the release rates decreased initially from the control (distilled water) as electrolyte concentration increased, until a minimum release rate was obtained. As the electrolyte concentration further increased the release rates similarly increased until a burst release occurred. These initial decreases in release rates were probably coincident with a decrease in polymer solubility, in that as the ionic strength of the dissolution medium is increased the cloud point is lowered towards 37°C. It may be seen from Table 5 that minimum release rates occurred when the cloud point was 37°C. At this point the pore tortuosity within the matrix structure should also be at a maximum. It is unlikely to be an increase in viscosity that retards release rates since Ford et al. [1] showed that viscosity has little effect on release rates. Any reduction in hydration, such as that by increasing the concentration of solute in the dissolution media or increasing the temperature of the dissolution media, will start to prevent gelation and therefore the tablet will cease to act as a sustained release matrix. 

Tablets may be formulated with coatings such as shellac, resin, or styrene-maleic acid copolymer. These coatings are insoluble in acid but dissolve readily at neutral or alkaline pH. Thus they are ideally suited to prevent drug release until the formulation has passed from the stomach into the small intestine. Preventing drug release in the stomach may protect drugs that are acid labile. It may also protect the patient from irritant substances like iron salts, diethylstilbo-estrol, and some anti-inflammatory agents. Release, and subsequent systemic availability of drugs from these formulations is likely to be highly sensitive to stomach emptying patterns.

The drug concerned was the salt of a weak base, with solubility in water about 2%. The base would precipitate out of solution at pH values above 5 or 6. The requirement was for a tablet formulation releasing the drug substance over about 3 hours. To ensure an adequate release rate in the neutral pH conditions of the small intestine it was decided to introduce an acidic ingredient, that would maintain a low pH within the dosage form and prevent formation of the insoluble base. Carbomer 934 was chosen as a matrix-forming polymer which would delay release but would also maintain the acidic environment within the tablet. 

The exclusive use of aspirin is as a medicine. It has three important properties as a drug. It relieves pain, reduces inflammation, and reduces fever. In addition to its effectiveness in treating these medical symptoms, it is inexpensive and available in a variety of forms, including chewable tablets, extended-release formulations, effervescent tablets, and even in chewing gums. Aspirin is often prescribed in low, daily doses as a preventative measure for individuals at risk for heart attack and stroke. 

Many of the published reports in the literature on the use of pH modifiers in solid dosage forms are for controlling the drug release from modified-release dosage forms, such as matrix tablets and coated tablets and beads (Gohel et al. 2003 Kranz et al. 1969 Naonori et al. 1991 Siepe et al. 2006 Streubel et al. 2000 Tatavarti and Hoag 2006 Thoma and Zimmer 1990). The pH modifiers have also been used to prevent disproportion of salts in tablets (Zannou et al. 2007). The use of pH modifiers in solid dispersion to enhance dissolution rate of drugs is, however, rather limited. 

Enteric coating materials are also used to prevent release of the drug substance in the stomach if the drug is either an irritant to the gastric mucosa or unstable in gastric juice. Table 7 lists enteric coating polymers commonly used in tablet formulations. The choice of of enteric coating material depends on its solubility. 

---