Immediate release products

When immediate-release products are used, die nurse administers die drug every 6 hours, hi some adults, intervals of 8 hours between dosing may be satisfactory. 

Fast-dissolving formulations (flash-dispersing) are not primarily intended to be for buccal delivery the issue here is that they may be taken without water. This causes an important difference in performance relative to ordinary immediate-release products, especially if the drug is in suspension. If the material is swallowed dry, it may adhere to the fundus area, where the amount of shear is low. This causes a significant fraction of the material to be retained resulting in tailing of the absorption phase and an apparently decreased AUC as the material is released over several hours. 

Management should be ATC dosing, with sustained-release product and an immediate-release product as for breakthrough pain. 

IM5-10mgq3-4h[Pg.633]

Dosingof selected agents by class fibrate (gemfibrozil 600 mg twice a day) niacin (1.5-3 g/day of immediate-release product) statin (simvastatin 10-40 mg/day if glomerular filtration rate [GFR] <30 mL/min, 20-80 mg/day if GFR >30 mL/min) bile acid sequestrant (cholestyramine 4-16 g/day). 

Dissolution indicates the rate-limiting step for compound absorption when drugs are administered orally. The solubility of a pharmaceutical compound represents its maximum concentration in an aqueous buffer. Additional compound will not dissolve above this concentration. The solubility value is often heavily dependent upon pH and temperature and is typically measured at physiologically important pH levels and body temperature. The standards for dissolution testing are determined by the United States Pharmacopoeia (USP). Testing typically requires sampling of a solution at 15, 30, 45, and 60 min for immediate-release products. /./Pl.C is ideally suited for use in conjunction with USP apparatus types I or II and can rapidly analyze multiple time points or replicate samples. 

Lawrence X, Jin T, Wang, Ajaz S, Hussain. Evaluation of USP Apparatus 3 for dissolution testing of immediate release products. AAPS Pharm Sci 2002 4(1) 1. 

Dressman JB. Dissolution testing of immediate-release products and its application to forecasting in vivo performance. In Dressman JB, Lennemas H, eds. Oral Drug Absorption Prediction and Assessment. New York Marcel Dekker, 2000 155-181. 

Individualize frequency of dosing -W Vr immediate-release products, dosing every 6 hours is generally required, especially in children intervals 8 hours or less may be satisfactory in adults. When converting from an immediate-release to a sustained-release product, the total daily dose should remain the same, and only the dosing interval adjusted. 

Sakr, A. and Andheria, M. (2001) A comparative multidose pharmacokinetic study of buspirone extended-release tablets with a reference immediate-release product. / Clin Pharmacol 41 886-894. 

As has been stated earlier, physical interactions can be either beneficial or detrimental to product performance. The distinction often depends on the particular application or context. For example, what may be beneficial for a prolonged release product may be detrimental in an immediate release product, and vice versa. This type of interaction can be between the drug and the excipient(s) or between two or... 

Bioavailability studies for IVIVC development should be performed with enough subjects to characterize adequately the performance of the drug product under study. In prior acceptable data sets, the number of subjects has ranged from 6 to 36. Although crossover studies are preferred, parallel studies or cross-study analyses may be acceptable. The latter may involve normalization with a common reference treatment. The reference product in developing an IVIVC may be an intravenous solution, an aqueous oral solution, or an immediate release product. 

Since nicotinic acid can cause unpleasant flushing and other symptoms of vasodilatation, attempts have been made to develop modified-release formulations. Modified-released nicotinic acid formulations may be better tolerated than the immediate-release formulation, because they reduce the vasodilatory effects of the drug. However, the low frequency of flushing produced by modified-release formulations may be offset by an increased risk of hepatotoxicity. Some reports have suggested a higher frequency of hepatic dysfunction with traditional modified-release nicotinic acid formulations compared with immediate-release products (2, 40). 

For immediate-release products, the most commonly used dissolution apparatus are the USP Apparatus 1 (basket) and USP Apparatus 2 (paddle). Usually, the Apparatus 1 is operated at 100 rpm and the Apparatus 2 at 50 rpm. However, it was suggested that the Apparatus 2 is operated at 75 rpm... 

Data from subjects who experience emesis during the course of a BE study for immediate-release products should be deleted from statistical analysis if vomiting occurs at or before two times median Tmax. In the case of modified-release products, the data from subjects who experience emesis any time during the labeled dosing interval should be deleted. 

Used in mild-to-moderate pain May use in conjunction with opioid agents to decrease doses ot each Regular alcohol use and high doses of acetaminophen may result in liver toxicity Care must be exercised to avoid overdose when combination products containing these agents ate used Drug ot choice in severe pain Use immediate-release product with SR product to control breakthrough pain in cancer patents... 

Use in severe pain No advantages over morphine Use immediate-release product witfi conlrolled-telease product to conlrol "breakthrough" pain in cancer or chronic pain patents Use in severe pain... 

An immediate release product would require some special feature to warrant the increased cost of production when compared to a conventional capsule or tablet. Therefore, the major commercial use of pellets prepared by extrusion/spheronization is in the preparation of controlled release products and there are several highly successful products available. In particular the ability to produce pellets with a high drug loading offers advantages over alternative methods of forming pellets. 

The BCS could be used as a framework for predictions when IVIVC could be expected for solid immediate-release products as summarized in Table 19.5. It is... 

A dissolution test procedure identified in the pharmacopoeia, generally a one time point dissolution test for immediate-release products and a three or more time points dissolution test for modified release products. multisource pharmaceutical products... 

Only one time-point should be considered after 85% dissolution from the comparator product. An f value of 50 or greater (50-100) reflects equivalence (less than 10% difference) of the two curves, and thus equivalence of in vitro performance of the two products. To allow the use of the mean data, the coefficient of variation should not be more than 20% at the earliest time-point (e.g. 10 minutes in the case of the example given for immediate-release products), and should not be more than 10% at other time-points. 

The BCS was initially developed to provide a scientific approach for the granting of biowaivers that is, for allowing drug developers to replace certain bioequivalence clinical studies by accurate in vitro dissolution data (Yu et ak, 2002 Kalantzi et ak, 2005). The BCS was initially designed for immediate release products that are absorbed throughout the gastrointestinal tract. In addition to... 

Class 1 drugs must have wide therapeutic index, and their dissolution must be rapid for an in vivo bioequivalence study to be waived. An immediate release product is considered rapidly dissolving when not less than 85% of the labeled amount of the drug substance is dissolved within 30 minutes of using USP Apparatus I at 100 rpm (or Apparatus II at 50 rpm) in a volume of 900 mL or less in each of the following media 0. IN HCl or simulated gastric fluid USP without enzymes, in a pH 4.5 buffer, and in a pH 6.8 buffer or simulated intestinal fluid USP without enzymes (29). 

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