Formulations stability issues

Traditionally, the oleyl diamines used in this particular application should have an Iodine Value (IV) of above 70 g I2 per 100 g. Lower IVs can result in chain lubricant formulation stability issues, which could lead to sediment in the final application, hence resulting in blocked spray nozzles. Many of the recent developments in cationic-surfactant-based chain lubricants have been a consequence of improving formulation stability and PET compatibility via the development of polyamine formulations and etherdiamine formulations. 

Establish the compatibility of the capsule shell and the capsule contents. Determine the hygroscopic nature of the capsule formulation. For example, a hygroscopic formulation (active ingredient and/or excipients) can pull water from the capsule shell, which could affect the Active ingredient—stability issues such as degradation and morphology changes... 

In the case where stability issues prevent the pursuit of the preferred formulation, then it becomes more important to optimize the dry granulation process to achieve an improved uniformity of drug as a function of particle size. For these cases, it is important to consider the impact of the optimized granulation on tableting performance. Although it is important to consider the commercial manufacturing efficiency, the process challenges that impact quality are of primary importance. 

If a compound is known to have chemical stability issues and is going to be administered in low dose, the best prevention is to ensure the highest degree of crystallinity of the bulk active ingredient delivered to the formulation and maintain it in the state with the highest ratio of drug to excipient possible. 

In order to achieve a sustained drug release and a prolonged therapeutic activity, nanoparticles must be retained in the cul-de-sac and the entrapped drug must be released from the particles at a certain rate. If the release is too fast, there is no sustained release effect. If it is too slow, the concentration of the drug in the tears might be too low to achieve penetration into the ocular tissues [208]. The major limiting issues for the development of nanoparticles include the control of particle size and drug release rate as well as the formulation stability. 

Like many other herbal extracts, valerian extract is very hygroscopic. Inclusion into tablets raises stability issues. Coatings reduce moisture absorption but often lead to tablet explosion or visual deterioration (black specs). Tablets formulated with 250 mg valerian extract, spray-dried lactose, and compressible starch were... 

Storage stability has generally been the more serious stability issue faced with therapeutic proteins. Storage stability can be extremely formulation-specific [15,30,32,33], and even with a knowledge of the major degradation pathways in solution, selection of the optimum formulation for a solid is far from obvious. We illustrate the sensitivity of stability to formulation details with studies of an important protein product, human growth hormone. 

ICH guidelines ° describe and discuss stability issues and testing requirement for NCEs and macromolecules. These guidelines provide manufacturers and CSOs with acceptance specifications for accelerated and long-term stability studies. In addition to the drug substance and drug product, stability assessment is frequently conducted on raw materials, key intermediates, formulation excipients, and packaging materials. 

The importance of identifying the mode of delivery to the lung (i.e., nebulizer, MDI, DPI) as early as possible cannot be overemphasized. A drug salt form selected assuming development of a propellant-based MDI suspension formulation may be wholly unsuited for application in an aqueous-based nebulizer suspension on the basis of solubility and crystal growth potential. Physicochemical properties and stability issues considered to be of importance in the development of inhalation formulations are discussed later, as they relate to the individual dosage forms. 

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