Evaluating the Taste Masking Ability of Two Novel Dispersible Tablet Platforms Containing Zinc Sulfate and Paracetamol Reconstituted in a Breast Milk Substitute.

Milk is often used as a dispersion medium for medicines administration in young children but its taste-masking ability is unknown. A human taste panel was conducted to assess the potential of infant formula milk (Aptamil® 1) to mask the taste of two model WHO priority medicines, zinc sulfate and paracetamol, manufactured as dispersible tablets. Simultaneously, the palatability of powder blends of the tablet platforms was assessed. Twenty healthy adult volunteers performed a swirl-and-spit assessment of placebos and API-containing blends in either a lactose-based or a mannitol-based dispersible tablet platform, reconstituted in 10 mL of either water or Aptamil® 1. Eighteen samples were rated for aversion using a 100-mm Visual Analogue Scale, grittiness using a 5-point Likert scale, and "acceptability-as-a-medicine" evaluated as: "Would you find this sample acceptable to swallow as a medicine?" with binary answers of Yes/No. The API-containing formulations were more aversive than the placebos; the paracetamol-containing samples being more aversive than zinc sulfate samples. The platforms themselves were not aversive. Non-gritty samples had four-fold greater odds of being acceptable as a medicine. Aptamil® 1 masked the taste of zinc sulfate in the mannitol-based formulation but did not mask the taste of paracetamol in either platform, suggesting a limited taste-masking ability, which may be API and formulation dependent.

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

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.

Mimicking the Impact of Infant Tongue Peristalsis on Behavior of Solid Oral Dosage Forms Administered During Breastfeeding.

An in vitro simulation system was developed to study the effect of an infant's peristaltic tongue motion during breastfeeding on oral rapidly disintegrating tablets in the mouth, for use in rapid product candidate screening. These tablets are being designed for use inside a modified nipple shield worn by a mother during breastfeeding, a proposed novel platform technology to administer drugs and nutrients to breastfeeding infants. In this study, the release of a model compound, sulforhodamine B, from tablet formulations was studied under physiologically relevant forces induced by compression and rotation of a tongue mimic. The release profiles of the sulforhodamine B in flowing deionized water were found to be statistically different using 2-way ANOVA with matching, when tongue mimic rotation was introduced for 2 compression levels representing 2 tongue strengths (p = 0.0013 and p < 0.0001 for the lower and higher compression settings, respectively). Compression level was found to be a significant factor for increasing model compound release at rotational rates representing nonnutritive breastfeeding (p = 0.0162). This novel apparatus is the first to simulate the motion and pressures applied by the tongue and could be used in future infant oral product development.

Characterising the disintegration properties of tablets in opaque media using texture analysis.

Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. This study has explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (P<0.0001) from one another for both tablet formulations using one-way ANOVA. Using the Tukey post-hoc test, the Sybedia Flashtab placebo tablets were found not to have statistically significant disintegration times from each other in human versus bovine milk (adjusted P value 0.1685).

Fabrication and in vivo evaluation of highly pH-responsive acrylic microparticles for targeted gastrointestinal delivery.

Acrylic enteric microparticles for oral drug delivery were prepared by an oil-in-oil emulsion solvent evaporation process. The novel use of sorbitan sesquioleate as a surfactant produced Eudragit L55, L and S (pH thresholds of 5.5, 6 and 7, respectively) microparticles of good morphology (spherical, smooth surfaced), size (<100microm) and size uniformity. The process was efficient (yield approximately 90%) and the encapsulated model drug (prednisolone) was in the amorphous form. The Eudragit L and S microparticles showed excellent pH-responsive drug release in dissolution studies (negligible drug release at pH 1.2; rapid drug release above the polymers' pH thresholds). In contrast, Eudragit L55 particles aggregated in fluid and showed poor control of drug release. In vivo in rats, Eudragit L microparticles released their drug load rapidly (T(max)<1h) and the C(max) and AUC were higher than those of a control suspension of prednisolone. Drug absorption from Eudragit S microparticles was low which was attributed to the fact that the threshold pH of Eudragit S was not reached in the rat intestine and drug release was therefore incomplete. It was concluded that although the rat is an inappropriate model for the investigation of Eudragit S microparticles, the positive results seen with the Eudragit L microparticles indicate its potential use in pH-targeted drug delivery.