Validation oral dosage form

T. Waaler, S. A. Sande, B. W. Muller, G. Schuller-Lisether, The influence of thermal neutron irradiation on the in vitro characteristics of ASA oral dosage forms—Validation of neutron activation, Eur J Pharm Biopharm 43 159-164 (1997). 

There are a number of FDA regulatory guidances that are associated with IVIVC development and validation, as well as the application of IVIVC to SUPAC. The specific IVIVC guidance for oral modified-release formulations was first published in September 1997 (1). There are several guidances on SUPAC, including those for both modified release (2) and immediate-release solid oral dosage forms (3). The recent... 

Skoug JW, Halstead GW, Theis DI, Freeman JE, Fagan DT, Rohrs BR. Strategy for the development and validation of dissolution tests for solid oral dosage forms. Pharm Tech 1996 20(5) 58-72. 

Ahmed, S. U., Naini, V, and Wadgaonkar, D. (2005), Scale-up, process validation and technology transfer, in Shargel, L., and Kanfer, I., Eds., Generic Drug Product Development Solid Oral Dosage Form, Marcel Dekker, New York, pp. 95-136. 

Solid oral dosage forms containing new chemical entities (NCEs) are commonly formulated into tablets or capsules as their first market image formulation. Subsequent drug product line extension development on these NCEs may evaluate more specialized drug delivery systems. Dissolution testing of standard oral tablets or capsules will commonly utilize the paddle or basket apparatus. In this chapter we focus primarily on the development and subsequent validation of dissolution testing methods that use these two devices. 

The certification/validation of excipients used in solid oral dosage forms is also extremely important [23]. Excipients can represent less than 1% of a tablet formula or as much as 99%. It is no less important to validate the critical characteristics of the 1% material than of an excipient used in larger quantities. Factors to be aware of are (1) the grade and source of the excipients, (2) particle size and shape characteristics, and (3) lot-to-lot variability. 

The guidelines contained within this chapter should be considered as part of a comprehensive validation program for solid oral dosage forms. The unique formulation or process characteristics of a particular product and the equipment available to manufacture that product may dictate the need for a specialized validation program. As such, the multidisciplinary validation team must identify the product and process characteristics that must be studied and incorporate specific validation tests to ensure that that product will meet all quality, manufacturing, and regulatory requirements. 

The process validation protocol of a new aerosol product should be written by a qualified manufacturing or validation specialist familiar with aerosols. Others experienced in oral dosage forms such as suspensions or solutions would also be helpful. These technical specialists may be within the research, validation, or technical support departments, since this work will be done prior to approval of a new product. Approval of the protocol should be given by quality assurance, quality control, production management, and research. 

Another professional organization headquartered in central Europe, APV (International Association for Pharmaceutical Technology, Mainz, Germany), developed the topic further in two seminars in Gelsenkirchen in late 1981 and early 1982 [6]. Speakers from industry demonstrated how validation could be applied to industrial activities and how a balance between resources allocation and results could be achieved. Oral dosage forms, topicals, and sterile products, as well as analytical methods during development, transfer, and production phases were discussed. 

In such cases, an appropriate reference to the indirect food additive regulations [27] is typically considered sufficient. This reference is considered valid for liquid-based oral dosage forms which the patient will take only for a relatively short time. 

Response Surface Methodology for Validation of Oral Dosage Forms... 

Where physical attributes of the API are critical (e.g., APIs intended tor use in solid oral dosage forms or suspensions), blending operations should be validated to show homogeneity of the blended batch. Validation should include testing for critical attributes (e.g., particle size distribution, bulk, and tap density) that may be affected by the blending process. 

This chapter will discuss the role of the analytical chemist in the preformulation process and highlight the methods that will need to be developed, validated and utilized to support these studies. An assortment of analytical techniques is needed to measure a number of critical quality attributes of the new molecular entity such as solubility, purity, and crystalline habit. The methods will be used to make important decisions such as the choice of salt form, or which sohd oral dosage form has the best probability of providing adequate exposure in an early phase clinical study. These analytical tools are critical to the decision that a pharmaceutical development organization uses to evaluate the first round of solid dosage form development prior to the availability of clinical data. 

For this calculation, it is unnecessary to assume that Vd and/or kei are the same for the two studies. It is only necessary that fe be the same in both studies. This is usually a valid assumption unless the drug undergoes a significant amount of first-pass metabolism in the gut wall or liver following oral administration or a significant amount of decomposition at an intra muscular (IM) injection site. When this occurs, the availability of the extravascular dosage form may appear to be low, but the fault will not lie with the formulation. The bioavailability will be a true reflection of the therapeutic efficacy of the drug product, and reformulation may not increase bioavailability. 

A report from a 1990 ASCPT/DIA/APS/FDA-sponsored workshop entitled 7n vitro/In vivo Testing and Correlation for Oral Controlled/Modified Release Dosage Forms (1990) concluded that, while the science and technology may not always permit meaningful IVIVC, the development of an IVIVC was an important objective on a product-by-product basis. Procedures for development, evaluation, and application of an IVIVC were described. Validation of dissolution specifications by a bioequivalence study involving two batches of product with dissolution profiles at the upper and lower dissolution specifications was suggested. 

In general, it is assumed that the oral absorption process follows Lrst-order kinetics. This assumption appears to be valid for majority of the drugs. The Lrst-order process can also satisfactorily describe the oral absorption process of some drugs with very poor water solubility. Sometimes, the inclusion of the absorption time lag may appear to be needed to account for the lag time for the dissolution of the drug substance from the dosage form into the aqueous media in the Gl tract. 

Food and Drug Administration. Guide to Inspection of Oral Solid Dosage Forms Pre/Post Approval Issues for Development and Validation. Rockville, MD Office of Compliance, Center for Drugs and Biologies (Jan. 1994). 

U.S. FDA. Guide to inspections of oral solid dosage forms pre/post approval issues for development and validation. Guide Indus Jan. (1994). 

H. Mark, G. E. Ritchie, R. W. Roller, E. W. Ciurczak, C. Tso, and S. A. MacDonald, Validation of a Near-Infrared Transmission Spectroscopic Procedure. Part A. Validation Protocols, /. Pharm. Biomed. Anal, 28,251 (2002). G. E. Ritchie, R. W. Roller, E. W. Ciurczak, H. Mark, C. Tso, and S. A. MacDonald, Validation of a Near-Infrared Transmission Spectroscopic Procedure. Part B. Application to Alternate Content Uniformity and Release Assay Methods for Pharmaceutical Solid Dosage Forms, /. Pharm. Biomed. Anal, 29,159 (2002). M. Blanco, M. Bautista, and M. Alcala, API Determination by NIR Spectroscopy across Pharmaceutical Production Process, AAPS PharmSciTech, 9,1130 (2008). A. Peinado, J. Hammond, and A. Scott, Development, Validation and Transfer of a Near Infrared Method to Determine In-Line the End Point of a Fluidised Drying Process for Commercial Production Batches of an Approved Oral Solid Dose Pharmaceutical Product, /. Pharm. Biomed. Anal, 54,13 (2011). 

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