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38 September 2018 Tablets & Capsules Still, it is important that companies always consider the shell material's potential interaction with the softgel's liquid fill. For example, certain shell colors can react with some API solutions, dramatically reducing the product's stability or resulting in leakage [4]. Production cost Cost is another factor that pharmaceutical companies must consider when deciding whether or not to use soft- gels. Capsule fillers can be expensive to install for a com- pany more accustomed to manufacturing traditional tab- lets [5]. Likewise, developing the liquid fill for a softgel pharmaceutical product can be time consuming and costly and is likely to involve specialty excipients. Pharmaceutical companies can minimize these costs by outsourcing softgel development and production to a contract development and manufacturing organiza- tion (CDMO) with expertise in and existing capacity for softgel formulation. Conclusion In many cases, a softgel can be the ideal delivery system that improves the bioavailability of a poorly soluble API. After the initial setup costs and formulation development, softgels are relatively inexpensive to mass produce. In addi- tion, they can minimize the amount of excipient required, deliver precise dosages, and make otherwise unpalatable medicines easier to swallow, aiding patient compliance. However, like all dosage forms, softgels are not suitable for all products. It is important that pharmaceutical devel- opers fully understand the stability characteristics and manufacturing considerations involved in making softgel products before selecting this dosage form. That being said, softgel expertise and production capacity is available, and skills in these areas are quickly becoming the bench- mark of a modern, full-service CDMO. T&C References 1. R. P. Scherer, "Apparatus for forming and filling capsules," US patent No. 2288327A, (1935). 2. R. P. Gullapalli, "Soft gelatin capsules (softgels)," Journal of Pharmaceutical Sciences, Vol. 99, Issue 10, pages 4,107-4,148, (2010). 3. G. Reich, "Formulation and physical properties of soft capsules," Pharmaceutical Capsules, pages 201-212, (2004). 4. H. I. Benza and W. L. Munyendo, "A review of progress and challenges in soft gelatin capsules formula- tions for oral administration", International Journal of Pharmaceutical Sciences Review and Research, Vol. 10, pages 20-24, (2011). 5. G. Cole, "Evaluating development and production costs: tablet versus capsules," European Journal of Pharmaceutical Sciences, Vol. 5, pages 17-26, (1998). Tomasz Bokas is European CMO sales manager at Saneca Pharma (+42 133 736 1111, www.saneca.com). appeal, and patient compliance. However, it is important that manufacturers understand softgels' strengths and weaknesses before choosing this dosage form. Drug delivery characteristics The primary reason pharmaceutical formulators and manufacturers use softgels is that this dosage form can effectively deliver poorly bioavailable APIs. According to some estimates, 40 percent of new chemical entities have poor biopharmaceutical properties, specifically due to low solubility [2]. Low solubility is a significant problem for drug devel- opers because insoluble compounds—those designated as Biopharmaceutics Classification System (BCS) Class II or IV—are poorly absorbed by the human body, ultimately impacting a product's efficacy. Softgels can help resolve this problem because APIs contained in a solution are more readily absorbed and reach the site of action more easily than solid-form APIs. Shell material Despite softgels' utility, there are a number of consid- erations manufacturers need to keep in mind when pro- ducing softgel formulations. One major manufacturing constraint is that the gelatin shell is highly water soluble. During production, water is used to make gelatin pour- able and after production the majority of the water is removed. However, the finished capsule shells still con- tain a water content of 4 to 10 percent [3]. In some respects, gelatin's solubility is an advantage. Because softgels rapidly dissolve when ingested, they are ideal for delivering fast-acting medicines. A drawback to gelatin's solubility is that it makes softgels very sensitive to heat and humidity. As a result, the shelf life of softgel for- mulations can vary considerably depending on storage conditions, which can pose potential stability problems for manufacturers and distributors in hot or humid climates. Gelatin's solubility also impacts the types of APIs for- mulators can use because the liquid fill must be oil-based rather than water-based to prevent it from interacting with the outer shell. This requires excipients that can dis- solve the API in an oily suspension. While gelatin—an animal-derived product—remains the most commonly used shell material, these solubility issues combined with demand for non-animal-based products have prompted companies to explore other shell materials. Alternatives are usually based on synthetic polymers or plant-derived hydrocolloids, with hydroxypropyl methylcellulose (HPMC) being one of the best-known examples. Softgel design Another reason that pharmaceutical companies choose softgel formulations is because the products can be tai- lored to improve patient compliance. For example, the shape of a softgel capsule can be modified to make it eas- ier for patients to swallow. Likewise, manufacturers can incorporate taste-masking technologies into capsule shells to make otherwise unpalatable medicines more pleasant.