Drug formulations solid oral

The dosage forms most commonly employed for pediatric formulations are liquids and chewable tablets. A perceived unpleasant taste is much more evident with these dosage forms than when a drug is administered as a conventional solid oral dosage form. Second, it is widely believed that children younger than the age of 6 years have more acute taste perception than older children and adults. Taste buds and olfactory receptors are fully developed in early infancy. Loss of taste perception accompanies the aging process. 

For formulations not meeting the criterion for very fast release of drug substance, similarity of profiles may be evaluated by model-independent or model-dependent methods as stated in the Guidance for Industry—Dissolution Testing of IR Solid Oral Dosage Forms (1,2). 

Motz SA, Schaefer UF, Balbach S, Eichinger T, Lehr CM (2006) Permeability assessment for solid oral drug formulations based on Caco-2 monolayer in combination with a flow through dissolution cell. Eur J Pharm Biopharm 66 (2) 286-295... 

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 extent of drug release from oral solid formulations is determined by the dissolution rates of drug, which is a function of aqueous solubility and particle sizes as shown in the following equation. 

Biobatch The lot of drug product formulated for purposes of pharmacokinetic evaluation in a bioavailabUity/bioequivalency study. For modified release solid oral, this batch should be 10% or greater than the proposed commercial production batch or at least 100,000 units, whichever is greater. 

In another example of a polyethylene glycol/surfactant, solid dispersion is presented by Dannenfelser et al. (2004) with a poor water-insoluble drug exhibiting only a g1i7iL aqueous solubility. At 40 mg/mL, the PEG 3350/polysorbate 80 solid dispersion exhibited similar exposure as that of a cosolvent-surfactant solution and a ten-time increase over a dry blend formulation, thus enabling a solid oral dosage form for clinical trials. 

Vasanthavada, M. and A. T. M. Serajuddin. Lipid-based self-emulsifying solid dispersidripid-n Based Formulations for Oral Drug Delivery Enhancing the Bioavailability of Poorly Vteter-Soluble Drugs, ed. D. J. Flauss, 149-183. New York Informa Healthcare. 

Figure 2.3 Solid oral formulation decision tree for low-dose drug product (<1 mg).

These practical issues of particle shape and dispersion are not intended to cast aspersions on the laser diffraction technique rather, these factors have been discussed to bring awareness around the analytical results that are obtained when these factors are present. Laser diffraction has proven itself to be a reliable, robust technique for particle size analysis. When the assumption of nonaggregated spherical particles is violated, there are clear manifestations in the calculated particle size distribution. When analyzing drug substances that are used in low-dose solid oral formulations, the impact of these manifestations can be particularly impactful as there is often a limited number of API lots to be used for method development. Therefore, the analyst must be aware of these issues prior to the commencement of method development to avoid these pitfalls. In addition to the information contained in ISO 13320, Snorek et al. have written a summary around the general practices of laser diffraction measurements in the pharmaceutical industry.19... 

Each of the aforementioned techniques is capable of measuring powder that would be used in low-dose, solid oral dosage formulations. The technique must be compatible with the drug substance, and must be capable of producing the information that is needed. For example, if the particle size distribution is needed to ensure dose content uniformity, photon correlation spectroscopy can only provide an average particle size. In this instance, laser diffraction or image analysis would be more suitable techniques. Table 13.1 contains a comparison of the techniques that have been discussed. 

For low-dose solid oral formulations, there may be considerable advantages to using IGC to measure the surface area of drug substances because the probe molecule can be tuned for the specific compound, and additional information can be obtained about surface chemistry. 

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