Preparation and Evaluation of a Dosage Form for Individualized Administration of Lyophilized Probiotics.

Probiotics have been used in human and veterinary medicine to increase resistance to pathogens and provide protection against external impacts for many years. Pathogens are often transmitted to humans through animal product consumption. Therefore, it is assumed that probiotics protecting animals may also protect the humans who consume them. Many tested strains of probiotic bacteria can be used for individualized therapy. The recently isolated Lactobacillus plantarum R2 Biocenol™ has proven to be preferential in aquaculture, and potential benefits in humans are expected. A simple oral dosage form should be developed to test this hypothesis by a suitable preparation method, i.e., lyophilization, allowing the bacteria to survive longer. Lyophilizates were formed from silicates (Neusilin® NS2N; US2), cellulose derivates (Avicel® PH-101), and saccharides (inulin; saccharose; modified starch® 1500). They were evaluated for their physicochemical properties (pH leachate, moisture content, water absorption, wetting time, DSC tests, densities, and flow properties); their bacterial viability was determined in conditions including relevant studies over 6 months at 4 °C and scanned under an electron microscope. Lyophilizate composed of Neusilin® NS2N and saccharose appeared to be the most advantageous in terms of viability without any significant decrease. Its physicochemical properties are also suitable for capsule encapsulation, subsequent clinical evaluation, and individualized therapy.

Commercially Available Enteric Empty Hard Capsules, Production Technology and Application.

Currently, there is a growing need to prepare small batches of enteric capsules for individual therapy or clinical evaluation since many acidic-sensitive substances should be protected from the stomach's acidic environment, including probiotics or fecal material, in the fecal microbiota transplantation (FMT) process. A suitable method seems to be the encapsulation of drugs or lyophilized alternatively frozen biological suspensions in commercial hard enteric capsules prepared by so-called Enteric Capsule Drug Delivery Technology (ECDDT). Manufacturers supply these types of capsules, made from pH-soluble polymers, in products such as AR Caps®, EnTRinsicTM, and Vcaps® Enteric, or capsules made of gelling polymers that release their content as the gel erodes over time when passing through the digestive tract. These include DRcaps®, EMBO CAPS® AP, BioVXR®, or ACGcaps™ HD. Although not all capsules in all formulations meet pharmaceutical requirements for delayed-release dosage forms in disintegration and dissolution tests, they usually find practical application. This literature review presents their composition and properties. Since ECDDT is a new technology, this article is based on a limited number of references.

Development and Comparison of Various Coated Hard Capsules Suitable for Enteric Administration to Small Patient Cohorts.

Pharmaceutical technology offers several options for protecting substances from acidic environments, such as encapsulation in enteric capsules or dosage form with enteric coating. However, commercial enteric capsules do not always meet limits for pharmacopeial delayed release, and the coating process is generally challenging. Preparing small enteric batches suitable for clinical use is, therefore, an unsolved problem. This experiment offers a simple coating process of DRcapsTM capsules based on hypromellose (HPMC) and gellan gum to achieve small intestine administration. In addition, DRcapsTM capsules were compared to hard gelatin capsules to evaluate the suitability of the coating method. Both capsules were immersed in dispersions of Eudragit® S 100, Acryl-EZE®, and Cellacefate at concentrations of 10.0, 15.0, and 20.0% and dried. Coated capsules were evaluated by electron microscopy, disintegration, and dissolution test with a two-step pH change (from 1.2 to 6.8, then to 7.5) to simulate passage through the digestive tract. DRcapsTM capsules coated with Eudragit® S and Cellacefate achieved acid resistance. While samples coated with Eudragit® S released their contents within 360 min at pH 6.8 (small intestine), regardless of polymer concentration, capsules with 15.0 and 20.0% coatings of Cellacefate released content at pH 7.5 (colon) within 435 and 495 min, respectively.