Formulation of an oral phosphorus solution adapted to neonatology
1. Pôle Pharmacie, Centre Hospitalo-Universitaire Grenoble Alpes, Grenoble, France
2. Université Grenoble Alpes, Faculté de. Pharmacie, TIMC UMR CNRS 5525, Grenoble, France
Background and objectives
In France, two specialities are indicated for the treatment of hypophosphatemic rickets: PHOSPHONEUROS® and PHOSPHATE SANDOZ® 500 mg. PHOSPHATE SANDOZ® 500 mg tablets require a compassionate access and are effervescent which is not suitable for the clinical needs of neonatal patients. PHOSPHONEUROS® has a high osmolality and an acidic taste despite the possibility of dilution, limiting patient compliance. Some neonates in the neonatal department of our hospital have fainting following its administration. The objective of this work was to formulate an oral phosphorus solution adapted to neonates in order to improve its acceptability and tolerance.
Material and methods
We compared different formulas: Joulié’s syrup (1), a formula developed by the Centre Hospitalo-Universitaire Sainte Justine (CHUSJ) (2) and a phosphorus formulation that we developed to the specific needs of neonatology. The criteria evaluated were organoleptic characteristics (evaluation of taste and texture), physicochemical characteristics that need to be compatible with the oral administration in neonates (osmolality < 600mOsm/Kg and 5<pH<8) to limit the risk of ulcerative colitis and to avoid dilution.
All the samples had a pH=5 except for the CHSJ solution with a pH=10. Concerning osmolality, only the CHUSJ solutions (469 mOsm/Kg) and the one developed by our unit (512 mOsm/Kg) were in conformity. PHOSPHONEUROS® and Joulié’s syrup needed to be diluted because of their high osmolalities, respectively 7840 and 2170 mOsm/Kg. The palatability test was conducted on a population of 20 adults, not representative of the target population. The formulas with the highest ratings were Joulié’s syrup (5.65/7) and our formula (5.175/7). The CHUSJ solution and the PHOSPHONEUROS® were not appreciated (scores < 4/7), judged respectively too salty and too acidic.
Discussion and conclusion
In order to improve the tolerance and acceptability of oral phosphorus solutions, we have developed a formulation adapted to the clinical needs of neonatology. Only this formulation presents physicochemical criteria compatible with the oral administration (osmolality < 600mOsm/Kg, 5<pH<8) to limit the risk of ulcerative colitis. In addition, it has satisfactory organoleptic characteristics. A physicochemical stability study will be carried out to make this preparation available in the department.
1. HUG. Sirop de Joulié, lien : https://pharmacie.hug.ch/infomedic/utilismedic/sirop_joulie.pdf.
2. CHUSJ. Suspension buvable de phosphore 10mg/ml.