Active ingredients and excipients

When an ophthalmic ointment is manufactured, all raw material components must be rendered sterile before compounding unless the ointment contains an aqueous fraction that can be sterilized by heat, filtration, or ionizing radiation. The ointment base is sterilized by heat and appropriately filtered while molten to remove extraneous foreign particulate matter. It is then placed into a sterile steam-jacketed kettle to maintain the ointment in a molten state under aseptic conditions, and the previously sterilized active ingredients) and excipients are added aseptically. While still molten, the entire ointment may be passed through a previously sterilized colloid mill for adequate dispersion of the insoluble components. 

The compatibility of the active ingredient with other active ingredients and excipients should be demonstrated. Preformulation study reports often provide useful relevant information. Preliminary stability study reports may be used as supporting data. 

Factors affecting the mix of active ingredients and excipients should be discussed. These should include particle size and shape, rugosity, charge, flow properties, and water content. Since the dose delivery for these products is dependent on air flow characteristics, an attempt should be made to establish an in vivo-in vitro correlation. 

The possibility of container-closure interactions should be considered, taking into account any admixture and dilution of products. Sorption of active ingredients and excipients should be considered as should leaching of container-closure components over the shelf life. Studies should extend to simulation of use. Pack components, administration devices (e.g., giving sets), and label adhesives should be considered. 

Issues similar to those discussed above for other dosage form types arise from the active ingredients and excipients proposed for use. 

There are two EPARs for eyedrops. Specific issues considered for these include container composition and tamper evidence, the optimization of the formulation and manufacture, preservative and preservation issues, and justification for the use of nonterminal sterilization processes. Many of the points concerning active ingredients and excipients are similar to those discussed above. Changes in formulation during the development process (e.g., for carbomers or surfactants) are mentioned. Particle size controls for suspension products are discussed. 

A number of oral solution or suspension products are included in the EPARs. Apart from the usual points of consideration for active ingredients and excipients, particular mention is made of possible precipitation of active ingredient when a solution is in use, the inclusion of excipients having a major impact on bioavailability, the need for flavoring to mask the taste of the active ingredient, relative potency compared with other routes of administration, preservation issues, dosing devices and the precision and accuracy of the dose delivered, and bioequivalence where formulations have been modified during the development process. 

Mouthwashes are aqueous concentrated solutions containing one or more active ingredients and excipients. They are used by swishing the liquid in the oral cavity. Approximately 15-30 ml. of mouthwash are used for single mouthful of rinse for about a minute. Mouthwashes can be used for therapeutic and cosmetic purpose. Therapeutic mouthwashes are used to reduce plaque, dental caries, gingivitis and stomatitis while cosmetic mouthwashes are used to reduce bad breath and it contains used antimicrobial and/or flavoring agent. Mouthwashes other than used for cosmetic purpose, should only be used under the direction of physician/dentist since it contains certain medicines. 

Chemical compound homogeneity is an important issue for pharmaceutical sohd forms. A classical spectrometer integrates the spatial information. In solid form analysis, use of a mean spectrum on a surface can be a drawback. For example, in the pharmaceutical industry it is important to map the distribution of active ingredients and excipients in a tablet so as to reveal physical interaction between the compounds and help to solve homogeneity issues. Spectroscopic imaging techniques that visualize chemical component distribution are thus of great interest to the pharmaceutical community. 

A typical reservoir system consists of a core (the reservoir) and a coating membrane (the diffusion barrier). The core contains the active ingredients and excipients, whereas the membrane is made primarily of rate-controlling polymer(s). The governing release mechanism is diffusion from the reservoir across the membrane to the bulk solution, and the one-dimensional release rate is described by Eqs. (4.4), (4.17), and (4.22).10,14 In addition,... 

The firm s investigation of Lot related to dissolution failures was inadequate in that it failed to evaluate the potential for and impact of dissolution failures in other lots that were manufactured using the same process, active ingredient and excipients. 

Jetzer, W., and Leuenberger, H. (1984), Determination of capping tendency in pharmaceutical active ingredients and excipients, Pharm. Acta Helv., 59(1), 2-7. 

U.K. IQA (1994) Pharmaceutical Supplier Code of Practice Covering the Manufacturing of Pharmaceutical Raw Material, Active Ingredients and Excipiants, Document Reference No. P00020, Issue 2, Institute of Quality Assurance, Pharmaceutical Quality Group. 

There is also the possibility of segregation of the constituents of the formulation after a homogeneous blend of active ingredient and excipients has been achieved. 

In a wet granulated product, particles are stuck together by the binder and so there is a much reduced chance of segregation. Because segregation is principally a function of differences in particle size between active ingredients and excipients, it is desirable that the size of the direct compression diluent matches that of the drug. This may not always be feasible. 

Mixing or blending is a critical process in the manufacture of dosage forms, especially in the production of tablets and capsules.The tablets or capsules prepared from the blend of poor mixing with active ingredients and excipients may fail the quality control test for content uniformity of the dosage forms. The acceptance limit according to the USP is based on the calculation of an individual assay of 10 tablets with a relative standard deviation equal to or less than 6%. Failure to meet the criteria results in rejection of the production lot. 

Another field of application, especially for ATR imaging, is that of pharmaceutical formulations. Here, in 2003, Chan et al. reported the first results on macro and micro ATR imaging of pharmaceutical tablets by characterizing the spatial distribution of active ingredients and excipients [19]. Further examples in this field are described in Chapter 10 of this volume. 

Before process validation can be started, manufacturing equipment and control instruments, as well as the formulation, must be qualified. The formulation of a pharmaceutical product should be studied in detail and qualified at the development stage, i.e., before the application for the marketing authorization is submitted. This involves preformulation studies, studies on the compatibility of active ingredients and excipients, and of final drug product and packaging material, stability studies, etc. 

Physical characteristics of the active ingredients and excipients can be modified. 

Cosmetic formulations are composed of active ingredients and excipients. Active ingredients are compounds directly related with the efficacy of the cosmetic product. Excipients can have different functions such as to facilitate the preparation of the formulation, to achieve the required physicochemical properties, to improve the efficacy or to provide stability to the finished product. On the other hand, active ingredients in some cosmetic formulations can act as auxiliary ingredients in other formulations. 

Because most pharmaceutical active ingredients and excipients absorb NIR radiation, studies utilizing NIR may provide certain advantages over traditional methods of assay for blend homogeneity or complement the... 

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