Esophageal transit of solid oral dosage forms - impact of different surface materials characterized in vitro and in vivo by MRI in healthy volunteers.

Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2 %, 11.1 %, and ≤5.6 % of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.

Parameters to consider for successful medication use in older adults - An AGePOP review.

Older adults are the main users of medicine and due to common multimorbidity they are often confronted with a complex medication management. This review article provides a brief overview on aspects of medication management, i.e., maintaining a stock of the required medicine, understanding and following the instructions for use, coping with the primary and secondary packaging, as well as the preparation prior to use. However, the main focus is on the drug intake itself and the review provides an overview of the current understanding of real life dosing conditions in older adults and geriatric patients. It elaborates the acceptability of dosage forms, in particular solid oral dosage forms as they represent the majority of dosage forms taken by this patient population. An improved understanding of the needs of older adults and geriatric patients, their acceptability of various dosage forms, and the circumstances under which they manage their medications will allow for the design of more patient-centric drug products.

Impact of Tablet Size and Shape on the Swallowability in Older Adults.

Older adults represent the major target population for oral medications, due to the high prevalence of multimorbidity. To allow for successful pharmacological treatments, patients need to adhere to their medication and, thus, patient-centric drug products with a high level of acceptability by the end users are needed. However, knowledge on the appropriate size and shape of solid oral dosage forms, as the most commonly used dosage forms in older adults, is still scarce. A randomized intervention study was performed including 52 older adults (65 to 94 years) and 52 young adults (19 to 36 years). Each participant swallowed four coated placebo tablets differing in weight (250 to 1000 mg) and shape (oval, round, oblong) in a blinded manner on three study days. The choice of tablet dimensions allowed for a systematic comparison between different tablet sizes of the same shape, as well as between different tablet shapes. Swallowability was assessed using a questionnaire-based method. All tested tablets were swallowed by ≥80% of adults, independent of age. However, only the 250 mg oval tablet was classified as well swallowable by ≥80% of old participants. The same was true for young participants; however, they also considered the 250 mg round and the 500 mg oval tablet as well swallowable. Furthermore, swallowability was seen to influence the willingness to take a tablet on a daily basis, especially for an intake over longer time periods.

Influence of Solid Oral Dosage Form Characteristics on Swallowability, Visual Perception, and Handling in Older Adults.

Swallowability, visual perception, and any handling to be conducted prior to use are all influence factors on the acceptability of an oral dosage form by the patient. Knowing the dosage form preferences of older adults, as the major group of medication end users, is needed for patient-centric drug development. This study aimed at evaluating the ability of older adults to handle tablets as well as to assess the anticipated swallowability of tablets, capsules, and mini tablets based on visual perception. The randomized intervention study included 52 older adults (65 to 94 years) and 52 younger adults (19 to 36 years). Within the tested tablets, ranging from 125 mg up to 1000 mg in weight and being of different shapes, handling was not seen as the limiting factor for the decision on appropriate tablet size. However, the smallest sized tablets were rated worst. According to visual perception, the limit of acceptable tablet size was reached at around 250 mg for older adults. For younger adults, this limit was shifted to higher weights and was dependent on the tablet shape. Differences in anticipated swallowability with respect to tablet shapes were most pronounced for tablets of 500 mg and 750 mg in weight, independent of the age category. Capsules performed worse compared to tablets, while mini tablets appeared as a possible alternative dosage form to tablets of higher weight. Within the deglutition part of this study, swallowability capabilities of the same populations were assessed and have been reported previously. Comparing the present results with the swallowing capabilities of the same populations with respect to tablets, it shows adults' clear self-underestimation of their ability to swallow tablets independent of their age.