Product reformulation, stability

Unsatisfactory Data If the stability data under the ICH conditions fall outside the acceptance criteria while data from the parallel study under the previously approved conditions or 25°C/ambient humidity, whichever applies, are satisfactory during the previously approved expiration dating period, and the added humidity is determined to be the cause for the stability failure, the product will still be considered to be in compliance with the regulatory specifications approved in the application. If the applicant decides to adopt the ICH conditions, a Changes Being Effected Supplement with a shortened expiration dating period or a Prior Approval Supplement with revised product specifications may be submitted where justified. Other measures (e.g., more protective container and closure or product reformulation) may be considered through a Prior Approval Supplement. 

The emergence of pure red cell aplasia as a complication of treatment with subcutaneous injection in the late 1990s was probably the result of the use of prefilled syringes with uncoated rubber stoppers in which the product was stabilized with polysorbate 80. Leachates from the stoppers most likely potentiated the immuno-genicity of the product leading to the production of neutralizing antibodies. Since the reformulation of the product, the incidence of PRCA has been steadily dropping. 

In using low-calorie sweeteners in various food products, die problems are not limited to flavor, but often much more importantly involve texture, acidity, storage stability, and preservability. among others. Acceptable nonnutritively sweetened products cannot be developed by the simple substitution of artificial sweeteners for sugars. Rather, the new product must be completely reformulated from the beginning. Three examples follow. 

Occasionally perfumes may cause destabilization of emulsions. This is an indication of inherent borderline stability of the emulsion system and should be remedied, wherever possible, by a change in the product formulation. Where this is out of the question, the only remedy is a laborious trial-and-error reformulation or replacement of the perfume compound. If high levels of phenylethyl alcohol or benzyl alcohol occur in the perfume, they may be the cause of the problem. 

Regulatory considerations also play a part in a decision whether or not to use the direct compression process. Several years may elapse between the finalizing of a tablet formulation and its marketing. During this period, stability testing of the product will have occurred. The formulator must be confident that a chosen direct compression diluent will still be available for a considerable time after product marketing otherwise reformulation with all its attendant delay and expense will be required. A number of direct compression diluents have been marketed that were withdrawn after only a few years because of lack of market penetration. 

Consequently, it can be inferred that products might have to be reformulated in order to improve their stability during storage under various conditions and environments. It should also be noted that the manufacturer may still chcmge excipients after registration, which may have implications on the stability cmd bioavailability of the product. The effect on other aspects of the product s safety and efficacy may have to be reviewed. 

Predesigned particles of impact modifiers are based on core-shell technology. Core is involved in impact modification and shell improves adhesion between PVC and impact modifier particles.Three major combinations are used methacrylate-butadiene-styrene, MBS, which has a core made out of butadiene-styrene copolymers and shell made out of methylmethacrylate-styrene copolymer, acrylic impact modifiers, AIM, which have a core made out of acrylic and shell from polymethylmethacrylate, and silicone-acrylic have multilayer structures with silicone-acrylic in the core. MBS has excellent compatibility with PVC, similar to ABS, which is used as an impact modifier of PVC, as well. In both cases of ABS and MBS, weather resistance is lacking, therefore they are used for indoor applications only. At the same time, MBS gives translucent to crystal clear products, whereas with AIM, only translucent products are possible. In order to improve optical properties of AIM, it has to be reformulated. For transparent products, the core is made out of acrylic-styrene copolymers. Comparing silicone and all acrylic impact modifiers, PVC containing silicone-based products has superior low temperature impact properties. The incorporation of silicone into an acrylic impact modifier provides excellent weatherability, and thermal stability. It has shown improved retention of impact after outdoor weathering in PVC. ... 

In 1998, Avnir and coworkers patented the interfacial polymerization process in which the mild sol-gel production of silica glass is combined with emulsion chemistry to form sol-gel spherical microparticles in place of irregular granules. In brief, the emulsion droplets provide a microreactor environment for the hydrolysis and condensation reactions of Si alkoxides. All sorts of molecules can be entrapped and stabilized in similar ceramic microparticles with broad control over the release rate for a range of applications (such as drug delivery, release of specialty chemicals and cosmeceutical/ nutraceutical, and beyond, Figure 18.1), with no need for reformulation for different molecules. 

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