Enteral Delivery of Pravastatin Sodium Tablets: Effect of Compounding into a Liquid Form and Co-Administration of Enteral Nutrition.

BACKGROUND: Compounding solid oral dosage forms into liquid preparations is a common practice for administering drug therapy to patients with swallowing difficulties. This is particularly relevant for those on enteral nutrition, where factors such as the administration procedure and co-administration of enteral nutrition play crucial roles in effective drug delivery. Due to the limited studies focused on this practice, the impact of co-administered nutrition remains unclear. METHODS: Pravastatin tablets were compounded into two liquid formulations and administered through three independent tubes for ten cycles. The drug amount was quantified upstream and downstream of the tubes both with and without different (fiber content) nutritional boluses. RESULTS: The compounding procedure did not lower the drug amount with respect to the original tablets. However, when the liquid formulation was pumped through the tubes, a statistically significant reduction in the pravastatin administered (between 4.6% and 11.3%) was observed. The co-administration of different nutritional boluses or the compounding procedure did not affect the general results. CONCLUSIONS: Pravastatin loss appears unavoidable when administered via the enteral tube. Although, in this case, the loss was of limited clinical relevance, it is important not to underestimate this phenomenon, especially with drugs having a narrow therapeutic index.

Tablet Splitting in Elderly Patients with Dementia: The Case of Quetiapine.

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization.

Rheological properties of cellulosic thickeners in hydro-alcoholic media: The science behind the formulation of hand sanitizer gels.

Cellulosic-based thickeners are commonly used in the preparation of hydro-alcoholic hand sanitisers. Yet, little is known about the behaviour of these polymeric dispersions in hydro-alcoholic mixtures. Here, we studied the dispersion ability and rheology of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and sodium carboxymethyl cellulose in water-ethanol mixtures. Hydroxypropyl cellulose formed transparent dispersions across the entire range of ethanol concentrations, while a critical ethanol concentration (CEC), above which dispersions became turbid, was found for all the other polymers. At and below the CEC, all the rheological parameters followed a bell-like shape profile as a function of ethanol concentration. Moreover, the molecular weight and degree of substitution of the polymers influenced the rheological properties. The CEC and rheological behaviour of the dispersions were both dependent on the ethanol/polymer and water/polymer interactions. As hand disinfectants should contain 60-95% ethanol, polymers of higher CEC, such as hydroxypropyl cellulose and hydroxypropyl methylcellulose, are recommended.

Potassium canrenoate compounding for administration via enteral feeding tubes: a physical and microbiological stability study.

BACKGROUND: Swallowing difficulties are arising in an increasing number of patients, especially in elderly people. When deglutition ability is completely compromised, enteral administration of a drug via feeding tubes is used. Licensed pharmacists have to compound the original solid forms to enable this drug therapy. OBJECTIVES: To evaluate the possibility of compounding original commercial tablets to produce a liquid formulation suitable for administering via a feeding tube. METHODS: Two liquid formulations containing potassium canrenoate 5 mg/mL were prepared: a standard solution obtained by solubilising raw material and an extemporaneous preparation obtained by dissolving film-coated 100 mg tablets. Spectrophotometric determinations (UV range) of the drug established chemical stability of the analyte up to 60 days. Samples were tested for microbial growth. Gravimetric quantifications of liquid formulations were used to check any weight loss during the different steps before enteral administration. RESULTS: UV data confirmed the chemical stability of potassium canrenoate up to 60 days. Samples showed no microbial growth. A higher weight loss was recorded in extemporaneous preparations than in the standard solution (10.7% vs 7.6%) according to the gravimetric quantification. CONCLUSION: It is possible to compound the original tablets into a liquid formulation suitable for administration via a feeding tube.

Potentially Inappropriate Prescribing of Oral Solid Medications in Elderly Dysphagic Patients.

Pharmaceutical formulations suitable for dysphagic patients are not always commercially available, motivating caregivers to crush tablets or open capsules to facilitate swallowing. Since this action may modify the characteristics of the medicine, it should be considered potentially inappropriate. This paper is the first to focus on how hospitalization affected the rate of potentially inappropriate prescriptions (PIPs) and the incidence of dosage form-related PIPs in elderly patients with dysphagia. Data was collected by reviewing patient medical records in the Italian National Research Center on Aging of Ancona. The therapy at admission and discharge was analysed in terms of: inappropriate drug associations, inappropriate drugs for dysphagic patients, inappropriate dosage forms and inappropriate dosage form modifications. Forty-one dysphagic patients with an average age of 88.3 years were included in the study and 451 prescriptions were analysed. PIPs were widespread at admission, and hospitalization did not improve the situation in a statistically significant manner. The most common PIPs identified (>80%) were related to dosage form selection and modification. This study highlights a clear need for continuing medical education about prescription appropriateness and modification of solid dosage forms in patients with dysphagia.

Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient's informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed.

Chemical and microbiological stability studies of an aqueous solution of pravastatin sodium salt for drug therapy of the dysphagic patients.

OBJECTIVE: This study is aimed to improve dysphagic patient compliance under therapy with cholesterol-lowering drugs. Patients suffering severe dysphagia, who do not feed independently, receive enteral nutrition through feeding tube and they need alternative oral route also for the administration of pharmacological therapy. This research deals with the development and stability (chemical and microbiological) of an aqueous solution of pravastatin sodium salt that will be administered orally directly in the feeding tube starting from commercial tablets. Tablets formulation is the only pharmaceutical dosage form available on the market for this type of drug. METHODS: Pravastatin sodium salt tablets are dissolved in a preserved sodium bicarbonate solution at the final concentration of 4 mg/mL. Samples are stored in two different conditions until 60 days. The samples are prepared for high-performance liquid chromatography analysis coupled to a diode array detector (HPLC-DAD), microbiological analysis and pH measurements. RESULTS: The chemical stability of the solution performed with HPLC-DAD analysis shows peaks' overlapping, which are characteristic of pravastatin, and correspondence of the concentration of the active ingredient in the solution. The detected values are analysed by one-way analysis of variance showing no statistically significant differences. Microbiological analyses proved that there is not microbial growth. By considering the dilution factor applied, it was possible to express the result as <10 CFU/mL in the two different culture media. CONCLUSION: This study demonstrated the possibility to reformulate pravastatin tablets as liquid pharmaceutical formulation for enteral administration with the aim of improving drug therapy in dysphagic patients.