Exploring Immersion Coating as a Cost-Effective Method for Small-Scale Production of Enteric-Coated Gelatin Capsules

The coating of a solid dosage form is a widespread process in the pharmaceutical industry because it offers a solution to many challenges encountered by scientists in the past. Indeed, there are various reasons for coating a dosage form [1,2]. Among these, coating can mask bad taste and odor [3,4], and it can protect the drug from oxygen, humidity, or other environmental factors [4,5]. The coating’s role can be aesthetic because it can improve the identification of the medicine (it has been proven that a colored film can aid in drug recognition, especially for elderly patients in polytherapy), and it can hide imperfections of the pharmaceutical form, particularly in the presence of APIs and excipients with different colors [6]. The coating can be also used to modify the drug release kinetics to obtain constant and prolonged release or ensure release in specific districts of the GI tract [7,8]. It is also possible, by combining coating with other modified release technologies, to obtain very complex release profiles, such as programmed ones [9]. One of the most common coatings used for modifying release applications is that applied to prevent the dissolution of the drug in the stomach and aim to release it in the intestine. This type of coating is usually called ‘gastro-resistant or enteric coating’, and it allows the administration of APIs targeted to the intestine or those that must avoid the stomach [10]. The enteric release of the drug is usually obtained by film coating using polymers with pH-dependent water solubility. Methacrylic acid–methyl methacrylate copolymers, cellulose derivatives with weak acid groups (such as cellulose acetate phthalate or hypromellose acetate succinate), or polyvinyl acetate phthalate are examples of polymers commonly used for enteric coating [1,2].

The industrial production of enteric film-coated dosage forms is a well-established process carried out using fluid bed or coating pan equipment. In almost all cases, the process involves the spray application of the coating solution and simultaneous drying, allowing to produce a large number of coated dosage forms in the same batch [1]. While industrial methods are highly effective for large-scale production, they are completely unsuitable for small batches, as required in personalized medicine and clinical production of coated dosage forms (e.g., hospital pharmacy or galenic preparation in a local pharmacy). The alternatives developed for these particular situations include two approaches: the use of capsule shells made of polymers having a pH-dependent dissolution or the design of inexpensive and easy-to-manage equipment that allows the coating of small batches. The first approach requires the use of the so-called Enteric Capsule Drug Delivery Technology (ECDDT). Despite these capsule shells having higher costs than traditional ones, they do not require additional equipment, and the preparations and formulations are exactly like the traditional ones. Several types of ECDDTs are now available on the market (such as Vcaps® Enteric and DRcaps®) [11]. In addition, the development of new ECDDTs represents an interesting topic for researchers in the pharmaceutical area [12,13].

Despite them potentially being the ideal solutions, the literature results are controversial, and in many cases, failures in obtaining enteric release profiles were reported [14]. The second approach is represented by equipment based on the immersion coating procedure (such as the ProCoater® by Torpac, Fairfield, NJ, USA), which allows the coating of small batches of oblong tablets or capsules by dipping these dosage forms into the coating solution [15]. These instruments enable the coating of a certain number of units simultaneously, and the coating solution can be used for several batches subsequently. However, dip coating presents several challenges for the formulator because the immersion of the dosage form in the coating solution is far more stressful than spraying or atomizing the solution on the pharmaceutical form. In addition, there are several variables to be optimized, such as the choice of the polymer, its percentage in the solution, the type and amount of plasticizer, the choice of solvents, and the formulation of the dosage form to be coated. Moreover, the success of the coating also depends on the process parameters, including the immersion time, the removal of excess liquid, and the type and duration of drying. Very few pieces of data are available for the process carried out through the immersion coating procedure, and most users rely on indications derived from studies performed with traditional spray-based methods. Among the published data, Moghimipour et al. [16] studied the effect of multiple coating layers of Eudragit FS 30D, an aqueous dispersion of methacrylic acid–methyl methacrylate copolymers, while Fülöpová et al. [17] evaluated the application of three types of enteric coating polymers on gelatin capsules or DRcaps®. Interestingly, the last study demonstrated that the coated gelatin capsules never achieved gastro-resistance, regardless of the type of polymer coatings and the concentration of the dispersions. In both cases, the coating process was not described.

The aim of this study was to assess the immersion coating of gelatin capsules using commercially available equipment to achieve standardized results. Two different grades of two enteric coating polymers were chosen, specifically Eudragit® S100, Eudragit® L100 (acrylic-based polymers), HPMC AS-MF, and HPMC AS-HF (cellulose-based polymers). Coating was carried out using organic polymer dispersions at two concentration levels. The capsules were filled with a formulation containing two model APIs with significantly different water solubility: paracetamol (AAP), defined as sparingly soluble by the European Pharmacopoeia (EP), and tramadol hydrochloride (Tram), reported by the EP as very soluble in water. The solubility of both drugs is pH-independent under the tested conditions (pKa of 9.38 and 9.41 for AAP and Tram, respectively [18,19]). The results were compared with those obtained through the ECDDT approach, using both single and cap-in-cap DRcaps® or Vcaps®.