Solid Dosage Form Considerations

Most pharmaceutical companies would rather have their new molecule enter the market as a tablet or capsule for a variety of safety, cost, and marketing considerations. As a result, almost 70% of all drugs administered today are in solid 

The particle size of a new drug substance is a critical parameter, as it affects every phase of formulation and its effectiveness. Appropriate particle size is required to achieve optimal dissolution rate in solid dosage forms, and to control sedimentation and flocculation in suspensions. Small particle size (2-5 gm) is required 

Micronization, where possible, allows an increase in the surface area to the maximum, which can make an impact on the solubility, dissolution, and as a 

Excellent instrumentation support and advice is available through Surface Measurement Systems (SMS) (1), manufacturer of DVS-Advantage and DVS-1000 and 2000 series of equipment for d3mamic vapor interaction studies. The DVS-FIT 

The injected gas molecules passing over the material adsorb on the surface with a partition coefficient K.  

---

If the areas under the curves are denoted by A, then (based on equal dose) All/Al is the fraction absorbed by oral route. Alll/All is the fraction efficiency of the solid dosage form. The reason for this latter is, of course, that the solid dosage form has to dissolve before the drug contained in it is available for absorption. It is the latter ratio that is important to the investigating pharmaceuticist, and therefore the outcome of the parenteral form is actually not a consideration from a formulation point of view. It is critical overall and if it is low, it may, at the point of parenteral data acquisition, be advisable to stop the program and evaluate the possibility of derivatives that would give better availability. 

In many diffusion problems of practical importance in the pharmaceutical sciences, such as intrinsic dissolution studies and drug release from solid dosage forms, the medium under consideration is not at rest. In addition to concentration changes due to diffusion, there are concentration changes by convection. External forces, such as pressure gradients and temperature differences, can cause convective flows. Although convection can also be caused by diffusion itself, our discussion is limited to convection caused by external forces, since convection produced by diffusion is negligible (less than 10%) for most pharmaceutical problems. 

Miller, L. A., R. L. Carrier, and I. Ahmed (2006). Practical considerations in development of solid dosage forms that contain cyclodextrinJ. Pharm. Sci., 96 1691-1707. 

Until recently, nonparenteral routes have failed to deliver sufficient quantities of ASO to be systemically therapeutic. The recent advent of novel oral delivery technologies, coupled with the increased tissue residence time for second-generation ASOs, allows oral delivery to achieve therapeutic levels for select systemic indications. This chapter will initially outline certain more conventional aspects of parenteral dosage forms, and then focus on formulation technologies that more specifically address local treatment. For the oral route, we will pass to the biopharmaceutic considerations for both local delivery to the gut and systemic delivery via absorption from solid dosage forms. Incumbent with the discussion on formulations is the need initially to overview the physico-chemical properties of ASOs, which in large part determine their biopharmaceutic characteristics. 

The processing and drug release properties can be partly or wholely affected by the physicochemical characteristics of meltable materials. The judicious choice of the meltable material to be used has considerable influences on the property and quality of the resulting solid dosage form. 

Attapulgite is widely used as an adsorbent in solid dosage forms. Colloidal clays (such as attapulgite) absorb considerable amounts of water to form gels and in concentrations of 2-5% w/v usually form oil-in-water emulsions. Activated attapulgite, which is attapulgite that has been carefully heated to increase its absorptive capacity, is used therapeutically as an adjunct in the management of diarrhea. 

Ward DR, Lathrop LB, Lynch MJ. Dissolution and compatibility considerations for the use of mannitol in solid dosage forms. ] Pharm Sci 1969 58 1464-1467. 

A considerable fraction of APIs u.sed in solid dosage forms exist in a highly crystalline state. Polymorphism is the ability of a compound to have two or more arrangements and/ or conformations of the molecules in the crystal lattice (9). Polymorphism is an important issue since the different polymorphs of a substance can exhibit differences, sometimes... 

The stability of solid dosage forms is usually very susceptible to the moisture content of the atmosphere in the container in which they are stored (see section 4.4.3) A linear relationship between log k and the water vapour pressure for vitamin A palmitate beadlets in sugar-coated tablets has been found. Similarly, a linear relationship between the logarithm of the rate constant for the decomposition of nitrazepam in the solid state and the relative humidity has been established (Fig. 4.f9). The need for consideration of the effect of moisture on stability has been stressed by Carstensen, who stated that stability programmes should always include samples that have been artificially stressed by addition of moisture. One purpose of a stability programme should be to define the stability of the dosage form as a function of moisture content. 

When processing auxiliaries such as copovidone in formulations for solid dosage forms, the particle size distribution can be of considerable importance. This particularly applies to the manufacture of tablets. However, it can also be important in solutions, e.g. film-coating solutions for tablets, as the dissolution rate and the dusting properties depend on the proportions of coarse and fine particles respectively. 

---