Dosage unit

It is shown, that for assay of substances and prepai ations the different approaches ( Confirming and Inspecting ) should be applied. The criteria to analytical procedures uncertainty for tests Uniformity of dosage units and Dissolution ai e developed. 

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. 

Goelen E, Lambrechts M, Geyskens F, Rymen T 1992) Development and performance characteristics of a capillary dosage unit with an in situ weight sensor for the preparation of known amounts of gaseous VOC s in air. Intern J Environ Anal Chem 47 217-225. 

The name and weight or measure of each active ingredient per dosage unit or per unit of... 

Most pancreatic enzyme supplements are enteric coated to release enzymes in the alkaline environment of the intestine this minimizes enzyme destruction in the stomach. Enteric-coated pancreatic enzyme supplements require fewer daily dosage units, but delivery of the drug to the site of action and effectiveness may be delayed by gastric emptying time.41... 

Contain the same quantity of active ingredient from one dosage unit to the next... 

Determination of the time for a tablet to disintegrate when immersed in some test fluid has been a requirement in most compendia for many years. For many years, it was the only test available to evaluate the release of medicaments from a dosage unit. We now recognize the severe limitations of such tests in assessing this property—hence, the introduction of dissolution rate requirements. 

A system was developed at Roche Laboratories whereby a sheet (or web ) was coated with a drug/binder mixture. The solid dosage units were then punched from the web [168]. This system was very flexible and amenable to immediate release and sustained-release technologies. However, due to the im-practicality of the system, it was abandonned in the mid-1980s and is only of historical significance. 

Generally increased cost per dosage unit Potential toxicity if system fails... 

Uniformity of dosage units. When the test is carried out as directed in the general procedure <905> meet the requirements. 

LSD. In 1971, about 274,000 LSD dosage units were seized in 1972, 340,000 in 1973, 490,000. In the first four months of this year, already 364,000 units had been seized. It is estimated that only a fraction of the amount of LSD available is seized. Sixty-four sets of LSD punches are known to have produced LSD for the illicit market during 1973, by contrast with the previously recorded high of 27 sets of punches known to have been operative in 1971. 

They seized about 80 pounds of MDA in various stages of production. It is estimated that one ounce of MDA can be made into 14,000 dosage units, which sell on the illicit retail market for 3 each. 

The Subscription represents the directions to the dispenser and indicates the type of dosage form or the number of dosage units. For compounded prescriptions, the subscription is written using English or Latin abbreviations. A few examples are provided as follows ... 

Sinkers are defined in USP as not more than a few turns of a wire helix.. .. Other sinkers may be used, but the analyst should be aware of the effect different types of sinkers may have on mixing (27). Sinkers can be barriers to dissolution when the wire is wound too tightly around the dosage unit. 

This acceptance scheme describes a stepwise procedure. If each of the six dosage units initially tested shows a dissolution rate of not less than Q + 5%, the test has passed at Stage... 

Stage Number of dosage units tested Complies if... 

Each single dosage unit is not less than Q + 5%... 

The arithmetic mean of the 12 dosage units (all units tested in Stages 1 and 2) is not less than Q and no single dosage unit is less than Q -15%... 

Independent of existing intra-lot variability, a sample size of six dosage units is generally recognized to suffice the needs of quality control (QC). In very early development less than six specimens may be used to create data, but as soon as possible tests should be run with at least n = 6. It is advisable to create statistically valid and sound data for manufacturing prototypes even at very early phases of development, in order to be able to identify formulations/batches with unwanted dissolution behavior. In the early phases of a drug product s development, formulations may not be of acceptable stability. This means that stability phenomena may mask... 

Failure to meet the acceptance criteria for dissolution for 12 dosage units. 

---