Non-disintegrating tablets

Infusion of fat into the ileum has been shown to cause a lengthening of the SITT—a phenomenon known as the ileal brake (27,28). However, the effect is generally modest (causing a delay of 30-60 min) and attempts to exploit this mechanism in drug delivery have had limited success. Dobson et al. (29,30) studied the effect of co-administered oleic acid on the small intestinal transit of non-disintegrating tablets. They showed a delay in SITT in over half of all cases, and a doubling of SITT in some instances, but in the other cases SITT was either unaffected or even reduced. Lin et al. (31) have also showed slowed GI transit in patients with chronic diarrhea by administration of emulsions containing 0, 1.6, and 3.2 g of oleic acid. Small intestinal transit in normal subjects was measured at 102 11 min, while the transit times in the patients treated with the three emulsions were, respectively, 29 3, 57 5 and 83 5 min. 

First and foremost, it is important to arrive at a thorough understanding of the compound s solubility behavior over the usual pH range encountered in the GI tract. Table 1 summarizes typical pH values in the GI tract in young, healthy individuals, as well as approximates residence times for pellets and (non-disintegrating) tablets in the various GI segments. 

Price JMC, Davis SS, Wilding IR (1993) Characterization of colonic transit of non disintegrating tablets in healthy subjects. Dig Dis Sci 38 1015-1021... 

Abrahamsson, B., Alpsten, M., Jonsson, U. E., Lundberg, P. J., Sandberg, A., Sundgren, M., Svenheden, A., and Toelli, J. (1996), Gastro-intestinal transit of a multiple-unit formulation (metoprolol CR/ZOK) and a non-disintegrating tablet with the emphasis on colon, Int. I. Pharm., 140,229-235. 

Khosla, R. Davis, S.S. Gastric emptying and small and large bowel transit of non-disintegrating tablets in fasted subjects. Int. J. Pharm. 1989, 52, 1-10. 

Figure 7.15 Gastric emptying time after administration with breakfast (a) and colon residence time (b) for a non-disintegrating tablet and pellet formulation in eight individual subjects CAbrahamsson et al. 1996).

TK Chukwu, A Chukwu. OK Udcala, Hydrophilic polymers as drug release modulators from non-disintegrating tablet matrices. Acta. Pharmaceutica. 42 181-188. 1992. 

Coupe A, Davis S, Evans D (1991) Correlation of the gastric-emptying of non-disintegrating tablets with gastrointestinal motility. Pharm Res 8 1281-1285... 

Our early scintigraphic studies, in which Tc-99m pellets and In-111 labeled non-disintegrating tables were dosed together, suggested differential transit through the lower gut (9). This was confirmed in later studies in which small tablets and... 

Although the non-heated tablets did not disintegrate, they did partially split on their horizontal axis after a few minutes in the dissolution medium. In contrast, the thermally treated tablets remained totally intact. This splitting phenomenon of the non-thermally treated tablets increased the surface area of the tablet which could contribute to the more rapid dissolution rate of drug as compared with the thermally treated tablets. The tablet formulation also contains 60%... 

The apparatus should be capable of allowing the evaluation of disintegrating, non-disintegrating, dense or floating tablets, or capsules and finely powdered drugs. 

Multiporous oral drug absorption system. A single-unit, immediate-release tablet formulation consisting of an inner core, containing active drug plus excipients, surrounded by a non-disintegrating, timed release coating. 

Fee JV, Grant DJW, Newton JM. The effect of surface coatings on the dissolution rate of a non-disintegrating solid (potassium chloride). J Pharm Pharmacol 1973 25 (SuppL) 149P-150P. Thomas WH. Measurement of dissolution rates of potassium chloride from various slow release potassium chloride tablets using a specific ion electrode. J Pharm Pharmacol 1973 25 27-34. Cartwright AC, Shah C. An in vitro dissolution test for slow release potassium chloride tablets. J Pharm Pharmacol 1977 29 367-369. 

Disintegrating as well as non-disintegrating USP calibrator tablets are available with a specified dissolution profile for each apparatus. These tablets are used to control the dissolution apparatus and to allow it to operate as intended, i.e., so that the hydrodynamic conditions are satisfactory. However, it should be noted that certain formulations might be more sensitive to such factors than are the calibrator tablets. 

Tablets are compressed preparations, and therefore, require a disintegrating agent to promote their disintegration by swelling, dissolving or becoming effervescent in contact with water. Furthermore, the hardness of a tablet is important. The Ph. Eur. requires that non-coated tablets disintegrate within 15 min in water. Currently available disintegrating agents allow the preparation of tablets which disintegrate within a few minutes.

Within the stomach an acidic environment exists, with a pH between 1.5 and 3.0 (with extremes between 1.0 and 5.0). In addition, digestive enzymes are present. The residence time in the stomach depends on the nutritional status and on the physical form of the medicine and may be highly variable. An active substance in solution, taken on an empty stomach, will pass the stomach quickly, usually within 30 min. A non-disintegrating large tablet, taken after a high-fat meal, may remain in the stomach for several hours. Absorption from the stomach plays a minor role in the total absorption, because of the relatively small surface of the gastric wall in relation to the stomach volume and the thickness of mucus layer and membrane. 

Tablets, orally disintegrating 10 mg (otc) A/ave/t (Wyeth Consumer), Thaminic Allerchews (Novartis), Dimetapp Children s ND Non-Drowsy Allergy (Wyeth)...

Table 3 List of commonly used tablet disintegrants Dosage Forms Non-Parenterals... 

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