Older adults using multi-dose dispensing exposed to risks of potentially inappropriate medications.

BACKGROUND: Multi-dose dispensing (MDD) of medications is a health technology designed to promote medication adherence and patient safety. MDD has been used as an alternative to ordinary prescription dispensing for patients, mostly elderly with high medication use. OBJECTIVE: To evaluate the initiation phase of the MDD service to older adults ≥65 years and assess wheter the medication use of the new MDD patients is appropriate in terms of drug related problems. METHODS: The European Union EU(7)-PIM list and the Inxbase databases were used for identifying potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs). The study sample consisted of a total of 208 patients aged 65-108 years who were involved in the MDD service (PharmaService Ltd.) in Finland in 2015-2016. Clinically significant differences of PIM and DDI occurrences were identified using a Pearson's chi-square test throughout the demographic groups under study. RESULTS: Results demonstrate that for 81% of the study participants, at least one medication from the EU (7)-PIM list was prescribed, and up to 64% of PIMs were clinically significant. According to the Inxbase database, five patients (2.4%) were prescribed category D clinically significant DDIs. Additionally, 61% of the patients saw an increase in the number of medications prescribed within six months after the initial MDD order. CONCLUSIONS: The results suggest that the MDD service should be accompanied by a regular medication review tailored to specific patient groups (i.e., older patients) to avoid potential DRPs.

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract.

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150-200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.

Bioavailability and in vitro oesophageal sticking tendency of hydroxypropyl methylcellulose capsule formulations and corresponding gelatine capsule formulations.

The overall aim of the present study was to widen our knowledge about the biopharmaceutical behaviour of novel hydroxypropyl methylcellulose (HPMC)-based two-piece capsules by comparing them with the classic hard gelatine capsules. Firstly, the tendency of the HPMC capsules to stick to isolated porcine oesophageal preparation was evaluated. The force needed to detach the HPMC capsules from the oesophagus was significantly lower than that for the gelatine capsules (P<0.001), which is evidently an advantage of this new dosage form. The second aim was to investigate the possibility of preparing sustained-release capsules using different powdered HPMCs as diluents (K100, K4M and K15M) and the effect of the molecular weight of HPMC powder on the in vitro and in vivo behaviour of the capsules. In addition to peroral drug administration also rectal dosing was applied. Two groups of eight healthy volunteers participated in randomised, cross-over, single-dose studies. One group was administered capsules orally and the other rectally. There were no marked differences in the bioavailability properties of either the oral or rectal HPMC capsules containing ibuprofen as model drug as compared with corresponding gelatine capsule formulations. Using different viscosity grades of HPMC powders as diluents it was possible to control the absorption rate of the model drug both from gelatine and HPMC capsules as far as the oral route was concerned. After rectal administration there were no statistically significant differences between the formulations containing different grades of HPMC powder. Only partial correlation was observed between the results of the bioavailability studies and the in vitro dissolution studies. From a biopharmaceutical point of view these two shell materials can be regarded as interchangeable.