Active ingredient solution/suspension

The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy, in which case additional safety and efficacy data are required. The same qualitative and quantitative composition only applies to the active ingredients. Differences in excipients will be accepted unless there is concern that they may substantially alter the safety or efficacy. The same pharmaceutical form must take into account both the form in which it is presented and the form in which it is administered. Various immediate-release oral forms, which would include tablets, capsules, oral solutions and suspensions, shall be considered the same pharmaceutical form for this purpose. 

Methyl parathion is marketed as a technical grade solution (80% methyl parathion) or in emulsifiable concentrate, wettable powder, ultra-low volume (ULV) liquid, dustable powder, and encapsulated suspension forms (HSDB 1999). The technical grade solution contains 80% active ingredient, 16.7%... 

Orally administered suspensions containing a wide class of active ingredients (e.g., antibiotics, antacids, radiopaque agents) are of major commercial importance. The solids content of an oral suspension may vary considerably. For example, antibiotic preparations may contain 125-500 mg solid drug per 5 mL or a teaspoonful dose, while a drop concentrate may provide the same amount of drug in only 1-2 mL. Antacid or radiopaque suspensions also contain relatively high amounts of suspended material for oral administration. The suspending vehicle can, for example, be a syrup, sorbitol solution, or gum-thickened water with added... 

The therapeutically inactive ingredients in ophthalmic solution and suspension dosage forms are necessary to perform one or more of the following functions adjust concentration and tonicity, buffer and adjust pH, stabilize the active ingredients against decomposition, increase solubility, impart viscosity, and act as solvent. The use of unnecessary ingredients is to be avoided, and the use of ingredients solely to impart a color, odor, or flavor is prohibited. 

The purpose of in-use stability studies is to establish the period for which a product intended to be used on more than one occasion may be used after reconstitution or dilution or the withdrawal of the first dose from the container without adversely affecting the integrity of the product and with the product retaining acceptable quality characteristics. This type of test can be applied to any multiple use product (e.g., sterile products in multiple-use containers, powders or granules including those used to produce oral solutions or suspensions) but is likely to be of particular importance in the case of products that are manufactured with an inert headspace gas, for products containing antioxidants to protect an active ingredient that is liable to oxidative decomposition, and for products that contain a volatile antimicrobial preservative. 

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. 

Inhalation solution and suspension drug products are typically aqueous-based formulations that contain therapeutically active ingredients and can also contain additional excipients. Aqueous-based oral inhalation solutions and suspension must be sterile (21 CFR 200.51). Inhalation solutions and suspensions are intended for delivery to the lungs by oral inhalation for local or systemic effects and are used with a specified nebulizer. Unit-dose presentation is recommended for these drug products to prevent microbial contamination during use. The container closure system for these drug products consists of the container and closure and can include protective packaging such as foil overwrap. 

Addition of the potent active ingredient to the formulation ingredients via the use of a solution or a suspension. Here, the active ingredient is either dissolved or suspended in the granulation vehicle, which is then used to granulate the dry excipient blend. 

For incorporation of the active ingredient inside a liquid matrix (as a solution, emulsion, or suspension), the first step of encapsulation is the dispersion of this liquid as droplets, which can be classified into four categories. 

SVI formulations are relatively simple, composed of the active ingredient, a solvent system (preferably aqueous), a minimal number of excipients present for reasons described later in this chapter, and the appropriate container and closure packaging system. If the active ingredient is unstable in solution or suspension, the product can be a dry powder, processed either by lyophilization or by sterile crystallization. 

Percentage weight in volume (% w/v) is the number of grams of drug in 100 mL of final product. This term is used for the concentrations of solutions, suspensions, etc. where the active ingredient is a solid for example, 5% dextrose infusion is 5 g of dextrose in 100 mL of final solution. 

Historically, wood preservatives have been thought of in terms of their solubility in either water or oil-type solvents (Ibach, 1999). Thus we have so called oil-bome and water-borne preservative systems. More recently that classification has become less relevant, because, with advances in formulation chemistry active ingredients can be formulated with either type of solvent, while others may be emulsions or suspensions. Water-based preservatives often include some type of co-solvent such as an amine or ammonia to keep one or more of the active ingredients in solution. Each solvent has advantages and disadvantages depending on the application. 

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