Poster presented at the 10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. 4-7 April 2016, Glasgow, UKN/

Aguiar, J. P.

Fernandes, A. I.

Fernandes, T. A.

Nese, C.

Pinto, J. F.

English

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 BACKGROUND   Nowadays, the need to formulate medicines specifically designed for children is imperative[1] and solid dosage forms are the first choice for providing the required drug stability and dose accuracy. Milk, as a worldwide accepted food, is proposed in this study as a platform to deliver drugs orally in pediatrics.    The main goals of this work were (a) the assessment of the properties of spray-dried fresh milk powders, (b) the evaluation of drug-milk interactions and (c) to ascertain the stability of the spray-dried milk powders.   MATERIALS AND METHODS     Quantification of theophylline in the spray-dried milk powders revealed that samples above 0.31 of theophylline fraction failed to have all drug present in the initial theophylline : milk solutions. During the spray-drying process, considerable losses of theophylline were observed for samples above 0.31 of theophylline fraction, which was in line with the results from the assays (HPLC).  3. Drug-milk interaction  Data from the calorimetric studies has shown that above 0.62 of theophylline content, regardless the fat content, revealed that the drug was not completely solubilized by milk components and, therefore, endotherms due to melting of theophylline started to appear in the thermograms. This finding was also corroborated by the microscopic analysis where theophylline crystals were predominantly observed in the samples mentioned earlier, indicating a limited capacity of milk to incorporate the drug.                 Figure 2: DSC thermogram of MFM powders atomized at 150 C and theophylline crystal observed by polarized light a) Spray-dried milk; b)Theophylline-milk 0.08:1; c) Theophylline-milk 0.16:1; d) Theophylline-milk 0.31:1; e) Theophylline-milk 0.62:1;  f) Theophylline-milk 1:1; g) Theophylline raw material   Due to an existing peak overlap of theophylline and spray-dried powdered milk components, the FT-IR results have shown that, when the milk components were present in higher fractions, the peaks in the amine region of the spectra due to theophylline were less intense (e.g. 3125-3120cm-1 region). No peak due to the resulting imine group from the Maillard’s reaction (1647-1630cm-1) was observed. Furthermore, no new bond formation was observed in any spectra (data not shown).  4. Stability  Shelf-life stability testing of powders has proven that the amount of drug in the spray-dried powders remained constant for 6 months. Regarding in-use stability of reconstituted powders in water, at room temperature, microbial content criteria[4] were met by all samples at 24h, regardless of their fat content. At 4ºC, criteria were met by all samples at 48h, but only LFM samples met the criteria, 7 days after reconstitution (Figure 3).                Figure 3: Stability in-use of drug-containing milk powders, after reconstitution in water.  Arrows indicate the last time point at which the compendial limits were met. REFERENCES  [1] European Medicines Agency (EMA). 5-year Report to the European Commission, 1–89 (2012). [2] Nijdam, J.J. and Langrish, T.A.G. The effect of surface composition on the functional properties of milk powders. J. Food Eng. 77, 919-25 (2005). [3] Nijdam, J.J. and Langrish, T. A. G. An Investigation of Milk Powders Produced by a Laboratory-Scale Spray Dryer. Dry Technol. 23, 1043–56 (2005). [4] European Pharmacopoeia 8th Edition Council of Europe: European Directorate for the Quality of Medicines and Healthcare, Strasbourg (2010)  ACKNOWLEDGEMENTS A.P. Alves de Matos is gratefully acknowledged for the SEM images. This work was supported by Fundação para a Ciência e a Tecnologia (PTDC/DTP-FTO/1057/2012), Lisboa, Portugal.  10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 4-7 April 2016, Glasgow, UK * Member of: Pharmaceutical Solid State Research Cluster (www.pssrc.org)  CONCLUSIONS   This study suggests that a spray-dried milk drug loaded powder is a promising platform to deliver drugs orally in pediatrics.   The powders obtained were stable after an easy extemporaneous reconstitution. iMed.Ulisboa: Research Institute for Medicines and Pharmaceutical Sciences CiiEM: Centro de Investigação Interdisciplinar Egas Moniz SPRAY-DRIED FRESH MILK POWDERS FOR ORAL DRUG DELIVERY IN PEDIATRICS   J. P. Aguiar1, T. A. Fernandes1, C. Nese2, A. I. Fernandes1, J. F. Pinto2*  1CiiEM, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, 2829-511 Caparica, Portugal 2iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal 1. Preparation of theophylline : milk systems Inlet Air Temperature (105, 130 and 150C) Theophylline Fraction Solutions of API : Fresh Milk  with different solids ratio 0:1, 0.08:1, 0.16:1, 0.31:1, 0,62:1 and 1:1 (w/w) 2. Spray-drying process 3. Powder Analysis Drug-Milk Interaction Properties of  Spray-dried powders Stability (in-use and shelf-life) Spray-drying Properties Particle Shape and Size Density Wettability Theophylline content (HPLC) FT – IR DSC Chemical Microbiological Yield Moisture Content 4. Data Analysis One-way ANOVA with Bonferroni post-hoc test; p<0.05 g) f) e) d) c) b) a) t0h t48h t24h t7 day Criteria met  regardless of the fat content  Criteria met by all samples Criteria met  only by LFM samples t28 day  content in solution throughout storage time Bacteria ≤ 103 CFU/ml  Yeasts ≤ 102 CFU/ml Absence of E. coli (ml) European Pharmacopoeia 8th 

Spray-dried fresh milk powders for oral drug delivery in pediatrics

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Spray-dried fresh milk powders for oral drug delivery in pediatrics

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