Pharmaceutical Ingredients

The quality attributes of meat products deteriorate due to the lipid oxidation during processing and storage. Lipid oxidation is responsible for development of primary and secondary oxidation products, reduction in nutritional quality, as well as changes in flavor, which can precipitate health hazards and economic losses in terms of inferior product quality. Lipid oxidation is a rather complex process whereby the unsaturated fatty acid fraction of membrane phospholipids is oxidized, and hydroperoxides are formed which are further susceptible to oxidation or decomposition to secondary oxidation products, such as short-chain aldehydes, ketones, and other oxidized compounds that may adversely affect the overall quality and acceptability of meat and meat products. Antioxidants are compounds that are capable of donating hydrogen (H·) radicals for pairing with other available free radicals to prevent the propagation reaction during the oxidation process. This effectively minimizes rancidity, retards lipid oxidation, without any damage to the sensory or nutritional properties, resulting in maintaining quality and shelf-life of meat products. However, intrinsic factors are available in live muscle to prevent lipid oxidation. These factors are often lost after slaughtering during conversion of muscle to meat, primary/secondary processing, handling, or storage of meat products, necessitating further supplementation with extrinsic antioxidants. For this reason, synthetic antioxidants, such as butylated hydroxytoluene (BHT), were extensively used to delay, retard, or prevent the lipid oxidation by scavenging chain-carrying peroxyl radicals or suppressing the formation of free radicals. However, because of the concern over the safety of these synthetic compounds, extensive work is being carried out to find novel and naturally occurring compounds to delay the oxidative degradation of lipids, improve quality, and maintain the nutritional value of foods. Thus, natural antioxidants have greater application potential in the meat industry because of the consumers’ acceptability over the synthetic antioxidants. However, the application of plant extracts, herbs, spices, and essential oils with antioxidant effects is still distant for the major reasons of limited data about their effects in different meat products. The meat industry is demanding antioxidants from natural sources to replace synthetic antioxidants because of the negative health consequences or beliefs regarding some synthetic antioxidants. Fruits, vegetables, by-products, and other plant materials provide good alternatives. Some of these antioxidants, apart from oxidation inhibition, may also affect other quality attributes positively or negatively, and ultimately affect consumer acceptability of the product. It has been shown that treatment with some natural sources can cause changes in the color of meat or meat products. Spices have shown to affect the flavor profile of treated meat and poultry products. Depending on the product, these flavors may be viewed as negatively or as positively by sensory panels. Some ingredients negatively affect the technological properties of meat and meat products, such as texture and emulsion properties. The safe edible use of these natural sources also depends on their health-related issues because some of these may also contain anti-nutritional or even toxicological factors. Thus, while establishing a new source of natural antioxidant for use in the meat and meat product at small, medium, or commercial level, following should be considered:  The in vitro antioxidant activity should be based on various different analytical techniques. The activity should also be confirmed in targeted products during various processing conditions; thus, the effects of cooking, pressure, product ingredients, and so on, on antioxidant potential should be confirmed.  The active ingredients/molecules of crude, concentrated or/and raw material should also be identified, and efficient conditions for extraction/separation of that particular molecule possessing potent antioxidant activity should be studied.  Apart from oxidation inhibition, other product attributes should also be considered. Thus, the overall cumulative effect of identified antioxidants should be evaluated in different products before reaching to a conclusion. For example, if one source is a very potent antioxidant, it can also affect the color and sensory properties negatively and lower the acceptability of the final product; then a proper conclusion should be drawn to establish these negative implications. Some natural antioxidants are also sensitive to light, temperature, and pH which results in reduction of antioxidant potential. Thus, future studies should also be directed towards exploring the storage and processing environment effects on the antioxidative potential of natural antioxidants.  Economics is the other main factor on which sustainability of any industry depends. Thus, economical extraction conditions should be well addressed relative to yield, time, infrastructure requirements, treatment materials, as well as the availability of natural sources. The correlation between economics of antioxidant use and economics of oxidation spoilage should also be considered before making any conclusion for the meat industry.  Mere conclusions based on in vitro, in vivo, or in producto antioxidant activity is not suitable when new unconventional antioxidant sources are discovered. Thus, nutritional and toxicological studies (in vitro/in vivo) must be done to ascertain the safe edible use of these natural sources. This is the most important point because the meat industry is rejecting synthetic antioxidants on the basis of negative health-related issues; thus, while accepting new natural antioxidants, these must be analyzed for the same health-related consequences.

Drug molecules with limited aqueous solubility are becoming increasingly prevalent in the research and development portfolios of discovery focussed pharmaceutical companies. Molecules of this type can provide a number of challenges in pharmaceutical development and may potentially lead to slow dissolution in biological fluids, insufficient and inconsistent systemic exposure and consequent sub-optimal efficacy in patients, particularly when delivered via the oral route of administration. Advances in the pharmaceutical sciences have led to the establishment of a number of approaches for addressing the issues of low aqueous solubility. These strategies for improving and maximizing dissolution rate include micronisation to produce increased surface area for dissolution, the use of salt forms with enhanced dissolution profiles, solubilisation of drugs in co-solvents and micellar solutions, complexation with cyclodextrins and the use of lipidic systems for the delivery of lipophilic drugs. Although these techniques have been shown to be effective at enhancing oral bioavailability, the success of these approaches is dependent at times on the specific physicochemical nature of the molecules being studied. Solubilisation technologies such as micellar systems are reliant on the acceptable solubility and compatibility of therapeutic molecules in a limited range of pharmaceutically acceptable excipients, whilst the increasing number of weakly ionisable and neutral molecules entering development constrains the opportunities for salt formation as a method of improving dissolution rate. Furthermore, whilst micronisation increases the dissolution rate of drugs through increased surface area, it does not increase equilibrium solubility. Often for drugs with very low aqueous solubility, the achieved increase in dissolution rate is insufficient to provide adequate enhancement of bioavailability. The potential for increased Van der Waals interactions and electrostatic attraction between ultrafine particles can also act to reduce the effective surface area for dissolution and therefore limit improvements in bioavailability. Crystal engineering approaches, which can potentially be applied to a wide range of crystalline materials, offer an alternative and potentially fruitful method for improving the solubility, dissolution rate and subsequent bioavailability of poorly soluble drugs. The ability to engineer materials with suitable dissolution characteristics, whilst maintaining suitable physical and chemical stability provides a strong driver for the utilisation of new and existing crystal engineering approaches to drug delivery system design. The challenges of low aqueous solubility provide an ideal situation for the application of crystal engineering techniques for improving bioavailability, whilst also developing stable and robust pharmaceutical products. The potential utility of crystal engineering as an approach for designing efficacious dosage forms for poorly soluble drugs is constantly reviewed and applications, benefits and drawbacks of this strategies are analysed. Crystal engineering is taken as the design of molecular solids in the broadest sense with the aim of tailoring specific physical or chemical properties, which may be used to manipulate the solubility and/or dissolution rate of the parent molecular components in the crystalline state. At the centre of these available approaches is the need to change surface and molecular assembly in equilibrium with a solution. Consequently, the recent developments in the study of molecular solids and topical issues such as habit modification, polymorphism, solvation, co-crystal formation (particularly, co-crystallisation) and surface modification, can help achieve good success rates and can become an emerging area of strategic importance to the pharmaceutical sector. The principles of crystal engineering are typically used to control crystal size, shape and crystalline form. Although the primary focus considers the crystalline state, the utility of amorphous materials, and their use in enhancing drug dissolution and bioavailability is also important. The precise control of crystallite size and shape provides notable improvements in the dissolution rate of hydrophobic active pharmaceutical ingredients (APIs). The crystal and particle engineering strategies have notable potential to strengthen the available methods for addressing problems of low aqueous solubility of drug substances. These methods are applicable not only to molecules of a specific physical and chemical nature, but to a wide range of crystalline materials, although a comprehensive knowledge of drugs at the molecular level is required to determine the appropriate approach to improving solubility and dissolution rate. The controlled production of ultrafine particles, particularly at sizes below 1 μm is becoming a favoured strategy for the pharmaceutical industry. In addition to the established comminution methods available to the formulator, new and emerging methods of controlled crystallisation provide an opportunity to produce highly pure crystalline drugs with narrow size distribution and desirable morphology. Although there are few disclosed examples of success in human subjects, there is sufficient evidence to demonstrate the potential benefits on dissolution in aqueous environments. The formation of molecular complexes and co-crystals is becoming increasingly important as an alternative to salt formation, particularly for neutral compounds or those having weakly ionizable groups. Despite lack of precedence in marketed products and concerns about the safety and toxicity of co-crystal forming agents, there is growing interest and activity in this area, which aims to increase the understanding of co-crystal formation and methods of preparation. Although, with some recent developments in crystal and particle engineering, established approaches such as the use of high-energy amorphous and metastable crystalline forms is still widespread. In particular substantial advancements in methods for isolating metastable crystalline have been achieved since the early days of chloramphenicol palmitate, whilst a greater understanding of the production and stabilisation of amorphous forms is also leading to a revolution in their use.