Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus

Abstract

Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32–51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch’s correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia.

Zinc delivery from non-woven fibres within a therapeutic nipple shield

“…In accordance with previous fibre studies by Gerrard et al (Gerrard et al, 2012), non-woven fibre mats (35% viscose, 65% polyester), provided from Bathfelt, Texel (Québec, Canada) were used as a delivery matrix. Two different types of fibre mats, placed within the same lipcontaining nipple shield device as previously applied for the evaluation of zinc delivery via rapidly disintegrating tablets by Scheuerle et al (Scheuerle et al, 2017), were investigated: a 235 gram per square meter (g m -2 ) felt with targeted thickness of 1.8 mm (referred to as fibre mat type A), and a 335 g m -2 felt with targeted thickness of 2.1 mm (referred to as fibre mat type B). An illustration can be found in Figure 2.…”

“…Zinc sulphate monohydrate was obtained from Sigma Aldrich (Dorset, UK), and preferred over elemental zinc based on its superior solubility and taste characteristics (Scheuerle et al, 2017). Human milk samples were supplied by the Queen Charlotte's and Chelsea Hospital Milk Bank (Imperial College Healthcare NHS Trust), and characterized as outlined in previous literature (Scheuerle et al, 2017), except that the fat content was calculated using an updated creamatocrit to fat correlation, published by Mitoulas et al (Mitoulas et al, 2002). Human milk used for experiments in this study had a protein content of 43.52 g l -1 , and a fat content of 16.51 g l -1 .…”

“…Based on literature about breastfeeding physiology (Black et al, 1998;Geddes et al, 2008;Macias and Meneses, 2011;Moral et al, 2010), and in accordance with previous work conducted using the simulation apparatus (Gerrard and Larson, 2013;Scheuerle et al, 2017), a flow rate of approximately 5.0 mL min -1 , a suction frequency of 1 suction/sec, and a temperature range of 33.4 -33.7°C, simulating the likely temperature of human milk in the infant's mouth, were chosen for all experiments. The pressure range and amplitude were adjusted to values of physiological relevance (Geddes et al, 2008).…”

“…Fractions were collected for a period of 40 s each with a total of 30 fractions, amounting to a total of 20 min. This duration corresponds to double the time of an average breastfeed (Geddes et al, 2008), and was chosen based on previously published breastfeeding simulation by Scheuerle et al to allow for comparative analysis (Scheuerle et al, 2017). All samples collected by the fraction collector were weighted using a Sartorius analytic balance (Epsom, UK), and subsequently stored at -80°C until further analysis.…”

“…To aid in-vitro testing of the TNS, a breastfeeding simulation apparatus was developed by Gerrard et al, simulating both the process of lactation and infant feeding by mimicking the average flow rates/patterns of milk during breastfeeding and the infant's suckling pressure . The apparatus was previously used to investigate release of a Sulforhodamine B dye and of zinc sulphate from rapidly disintegrating tablets into human milk (Gerrard et al, 2012;Scheuerle et al, 2017). The capability of non-woven fibres to release APIs into human milk was previously shown by Gerrard et al, who investigated the delivery of Sodium Dodecyl Sulphate (SDS) from loaded non-woven fibres (Bathfelt, Texel, Québec, Canada) located within a Sinnex filter holder, but without the use of breastfeeding simulation (Gerrard et al, 2012).…”