Tablet formulation particle size reduction

Particle size and particle size distribution studies are important for drugs that have low water solubility. Particle size reduction by milling to a micronized form increased the absorption of low aqueous solubility drugs such as griseofulvin, nitrofurantoin, and many steroids. Smaller particle size results in an increase in the total surface area of the particles, enhances water penetration into the particles, and increases the dissolution rates. With poorly soluble drugs, a disintegrant may be added to the formulation to ensure rapid disintegration of the tablet and release of the particles. 

Tablets and other drug formulations often comprise the active pharmaceutical ingredient (API) and pharmacologically inert carrier substances, or excipients, which bind, stabilize, and assist absorption of the drug by the body, or simply add bulk to APIs in low dosages. Common excipients are inorganic phosphates and organic compounds such as lactose, cellulose, and polyethylene glycol. Particle size reduction by micronization or milling can provide the energy to transform an API into undesirable polymorphs or...

If a low-dose dmg (< 1 mg per dose unit) is formulated as tablets or capsules, it can be very difficult to uniformly distribute a trace amount of dmg substance into a single unit dose, especially when direct compression is selected as the manufacturing platform. Major factors controlling the degree of homogeneity of the final blend are the mean particle size and the size distribution of dmg substance. It is often difficult to determine whether these factors are suitable for preparation of a low-dose dmg product.2 Generally, reduction of dmg substance particle size by milling or microni-zation is essential for a low-dose dmg product to meet the USP content uniformity criteria for tablets and capsules.3... 

Reduction in particle size, however, is not always desirable. For example, Slow K tablets incorporate a matrix that slowly releases potassium in order to minimize GI tract irritation. Simularly, Macrodantin is a formulation of large crystals of nitrofurantoin, which will dissolve slowly and thereby minimize irritation. 

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