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DIAZOXIDE 10MG/ML ORAL SUSPENSION AS A COST-EFFECTIVE ALTERNATIVE TO THE COMMERCIAL PREPARATION (submitted in 2019)

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European Statement

Production and Compounding

Author(s)

Beatriz Sánchez Sanz, Iván González Barrios, Siria Pablos Bravo, Sara Ortiz Pérez, Cristian Rosas Espinoza, María Arrieta Loitegui, Francisco Martínez de La Torre, Dolores Canales Sigero, José Miguel Ferrari Piquero

Why was it done?

The objective is the elaboration of a formulation as a cost-effective alternative to the diazoxide oral suspension not commercialised in Spain, to treat patients with hyperinsulinaemic hypoglycaemia.

What was done?

Diazoxide is the first line therapy in infants with hypoglycaemia due to hyperinsulinism. A formulation to facilitate the dosage in newborns has been developed due to the increasing demand at our Hospital.

How was it done?

To evaluate the solubility, a research on Pubmed was executed including terms such as “diazoxide AND solubility” and “tiazides AND solubility”. To determine the stability, the agreement approved by the “Pharmacotechnics Group of the Spanish Society of Hospital Pharmacy” concerning the viability of the non-sterile oral formulations was reviewed. In terms of effectiveness, a retrospective observational study was conducted. Demographic and clinical (duration of the therapy and blood sugar levels 24 hours after first administration, sorted as “sensitive” if those levels were over 60mg/dL) variables were collected.

What has been achieved?

Carboxymethyl cellulose gel 1.5% (CMC) was evaluated as suspending agent, with adequate results. The steps to compounding the formulation of diazoxide 10mg/mL oral suspension were: 1. Four capsules of 25mg were opened and spread over a mortar. 2. 10ml of CMC was measured on a test tube. 3. CMC was added slowly over the powder while stirring the mixture to obtain a homogenized milky creamy. 4. Suspension was stored in an amber bottle. Following our stabilities studies and the lack of preservatives, an expiration date of seven days at ambient temperature was assigned. In our hospital, seven neonates (four males) aged 5.8±2.3 days have been treated with this oral suspension, for an average period of 28 days. Six of them were classified as “sensitive” with levels of 105±30mg/dL while one showed no improvement. Analysing the global expense, one pack of 100 capsules costs €21. Thus, 1 unit of our suspension 10mL cost €0.84 versus 1 bottle of 30mL (€473); the savings are remarkable.

What next?

The preparation constitutes a suitable alternative by using a simple and cheap technique since its introduction. In the future, full studies of stability must be designed to prolong its period of validity and monitor its security.

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