Dissolution tablet

In developing a detergent tablet, the key concerns for the process engineer is to achieve the optimum balance of strength to dissolution. Tablet strength is important for packing operations in the plant and subsequent distribution to the trade and dissolution is critical for the performance of the product and to avoid highly undesirable product residues at the end of the wash. In addition, there are also a number of less obvious factors to be considered such as... 

Ghdants are needed to faciUtate the flow of granulation from the hopper. Lubricants ensure the release of the compressed mass from the punch surfaces and the release/ejection of the tablet from the die. Combinations of siUcas, com starch, talc (qv), magnesium stearate, and high molecular weight poly(ethylene glycols) are used. Most lubricants are hydrophobic and may slow down disintegration and dmg dissolution. 

Osmotic Control. Several oral osmotic systems (OROS) have been developed by the Alza Corporation to allow controUed deHvery of highly water-soluble dmgs. The elementary osmotic pump (94) consists of an osmotic core containing dmg surrounded by a semi-permeable membrane having a laser-drilled deHvery orifice. The system looks like a conventional tablet, yet the outer layer allows only the diffusion of water into the core of the unit. The rate of water diffusion into the system is controUed by the membrane s permeabUity to water and by the osmotic activity of the core. Because the membrane does not expand as water is absorbed, the dmg solution must leave the interior of the tablet through the smaU orifice at the same rate that water enters by osmosis. The osmotic driving force is constant until aU of the dmg is dissolved thus, the osmotic system maintains a constant deHvery rate of dmg until the time of complete dissolution of the dmg. 

In-vitro bioavailahility tests usually form part of the criteria for evaluating the individual batches of a product. These are based on monitoring the rate of release of the drug substance from the pharmaceutical form, usually by observing the dissolution rates of tablets or capsules. 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

Note on GMPs The assays are conducted on individual dosage units (here tablets) and not on composite samples. The CU test serves to limit the variability from one dosage unit to the next (the Dissolution Rate test is the other test that is commonly used). Under this premise, outlier tests would be scientific nonsense, because precisely these outliers contain information on the width of the distribution that one is looking for. The U.S. vs. Barr Laboratories Decision makes it illegal to apply outlier tests in connection with CU and DR tests. This does not mean that the distribution and seemingly or truly atypical results should not be carefully investigated in order to improve the production process. 

Figure 4.50. Cumulative dissolution results. Two experimental tablet formulations were tested against each other in a dissolution test in which tablets are immersed in a stirred aqueous medium (number of tablets, constructional details and operation of apparatus, and amount of medium are givens). Eighty or more percent of the drug in either formulation is set free within 10 minutes. The slow terminal release displayed by formulation B could point towards an unwanted drug/excipient interaction. The vertical bars indicate ymean - with Sy 3%. A simple linear/exponential model was used to approximate the data for the strength 2 formulation. Strengths I and 3 are not depicted but look very similar.

Figure 4.52. Coefficients of variation that reflect both tablet to tablet and analytical variability. For formulation B, particularly strengths 2 and 3, the drop in CV with higher cumulative release (a - b) is marked, cf. Fig, 4.50. When the dissolution rate is high, individual differences dominate, while towards the end analytical uncertainty is all that remains. The very low CVs obtained with strength 3 of formulation A ( 0.7-0.8%, data offset by +10% for clarity) are indicative of the analytical uncertainty. Because content uniformity is harder to achieve the lower the drug-to-excipient ratio, this pattern is not unexpected.

The Cadila system [13] has been designed to formulate tablets for drugs based on their physical (solubility, hydroscopicity, etc), chemical (functional groups), and biologically interrelated (dissolution rate) properties. The system first identifies the desirable properties for optimum compatibility with the drug, selects those excipients that have the required properties, and then recommends proportions based on the assumption that all tablet formulations comprise at least one binder, one disintegrant, and one lubricant. Other... 

Sodium bicarbonate tablets are administered in increments of 325 and 650 mg tablets. A 650 mg tablet of sodium bicarbonate contains 7.7 mEq (7.7 mmol) each of sodium and bicarbonate. Sodium retention associated with sodium bicarbonate can cause volume overload, which can exacerbate hypertension and chronic heart failure. Patient tolerability of sodium bicarbonate is low because of carbon dioxide production in the GI tract that occurs during dissolution. 

A drug should always be ingested with a cup of water ( 8 oz) to insure easy transit down the esophagus and to provide fluid for disintegration and dissolution. Whether or not the drug should be taken on an empty stomach (e.g., enteric-coated tablets) or with food will depend upon the specific drug as noted above. 

Diarrheal conditions may decrease drug absorption as a result of reduced intestinal residence time. The absorption of several drugs was decreased in response to lactose- and saline-induced diarrhea [145]. Digoxin absorption from tablets was impaired in one subject who developed chronic diarrhea as a result of x-ray treatment [146]. Abdominal radiation or the underlying disease has been shown to reduce digoxin and clorazepate absorption [147]. A dosage form that provides rapid drug dissolution (e.g., solution) may partially resolve this problem. 

TR Bates, JM Young, CM Wu, HA Rosenberg. pH-dependent dissolution rate of nitrofurantoin from commercial suspensions, tablets and capsules. J Pharm Sci 63 643-645, 1974. 

CE Blezek, JL Lach, JK Guillory. Some dissolution aspects of ferrous sulfate tablets. Am J Hosp Pharm 27 533-539, 1970. 

Returning to Fig. 6, it can be seen that the oral administration of two 15-mg tablets of propantheline 1.5 hours before atenolol delayed the rate of availability of this p-blocker, while increasing its extent of availability [11]. This increased extent might be due to more complete dissolution of the drug, resulting from its increased time in the gastrointestinal tract. 

Figure 13 compares the dissolution rate of pure phenacetin particles with the granulated particles of the same size and with tablets prepared from these granules. These comparisons were made by using... 

The effect of particle size reduction on the bioavailability of nitrofurantoin was shown in Fig. 4. The microcrystalline form (< 10 pm) is more rapidly and completely absorbed from the tablet dosage form than is the macrocrystalline form (74-177 pm) from the capsule dosage form. This is not a completely satisfactory illustration of the effect of particle size on the rate and extent of availability, since other manufacturing variables have not been held constant. Nevertheless, it does suggest some correlation between particle size, dissolution rate, and rate of availability. 

Fig. 13 Rate of dissolution of phenacetin from powder, granules, and tablets in diluted gastric juice (Surface Tension, 42.7 dyn/cm pH 1.85). 0> Phenacetin Powder , Phenacetin Granules , Phenacetin Tablets. (From Ref. 17.). 

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