Homogeneous drugs

Precision (Repeatability). To evaluate the repeatability as specified in the quantitative method of heavy metals in the drug substance, the drug substance samples are treated according to the test solutions and the control solutions preparation method selected from methods 1 to 4 of Heavy Metals Limit Test in JP. Take five or six aliquot samples collected from a single lot of homogeneous drug substance and determine the quantity of heavy metal in each sample aliquot using the prepared test and control solutions. The data obtained are statistically analyzed. 

Take five or six aliquot samples from a single lot of homogeneous drug substance. The sample amount is equal to that specified in the limit test method in the Specifications and Testing Methods. ... 

Egermann H, Kemptner I, Pichler E. 1985. Effects of interparticulate interactions on mixing homogeneity. Drug. Dev. Ind. Pharm. 11 663-676. 

Homogeneous drugs with A 0 their kinetics can be described homogeneously with what we will call compartmental models. These drugs are characterized by small or medium volumes of distribution. 

The techniques for predicting the chemical stability of homogeneous drug systems are well defined. " The formulation chemist should consider both the pH-solubility profile and the pH-stability profile when selecting the optimum pH for formulation of the liquid oral dosage form. For example. Figs. 3 and 4 show the... 

Organic chemists often use enantiomencally homogeneous starting materials for the synthe SIS of complex molecules (see Chiral Drugs p 296) A novel preparation of the S enantiomer of compound B has been descnbed using a bacterial cyclohexanone monooxygenase enzyme system... 

For a continuous SMB process, the specific identified amount or batch produced is defined by unit of time in such a way that ensures a homogeneous material and quality within specified limits. In the case of a continuous SMB production run a batch is defined by the amount produced in a fixed time interval. A time limitation during manufacturing using SMB is established by the same fixed time interval as the batch. The duration of the production phase is thus established, which does not affect the quality of the drug substance [66]. 

Process validation should be extended to those steps determined to be critical to the quality and purity of the enantiopure drug. Establishing impurity profiles is an important aspect of process validation. One should consider chemical purity, enantiomeric excess by quantitative assays for impurity profiles, physical characteristics such as particle size, polymorphic forms, moisture and solvent content, and homogeneity. In principle, the SMB process validation should provide conclusive evidence that the levels of contaminants (chemical impurities, enantioenrichment of unwanted enantiomer) is reduced as processing proceeds during the purification process. 

A key element in planning and conducting clinical trials is to ensure that they have scientific validity and objectivity. This is particularly relevant with respect to Phase II and III studies, where it is desired to demonstrate a positive benefit to risk outcome. Responses to a drug among a patient population are rarely homogeneous and clear-cut. Thus, sound statistical principles must be applied in order to be able to distinguish significant effects from random events. 

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). 

Talsma, H., Ozer, A. Y., van Bloois, L., and Crommelin, D. J. A. (1989). The size reduction of Uposomes with a high pressure homogenizer (Microfluidizer). Characterization of prepared dispersions and comparison of conventional methods. Drug Dev. Indust. Pharm.. 15, 197-207. 

Solubility is a fundamental characteristic of drug candidates. In synthetic chemistry, low solubility can be problematic for homogeneous reactions, and in precUni-cal experimental studies, low solubility may produce experimental errors or precipitation. 

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