Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial
A new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens (0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to (i) prepare low-dose melatonin hard...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177917300461 |
| _version_ | 1818407737581633536 |
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| author | Samira Filali Charlotte Bergamelli Mamadou Lamine Tall Damien Salmon Diane Laleye Carole Dhelens Elhadji Diouf Christine Pivot Fabrice Pirot |
| author_facet | Samira Filali Charlotte Bergamelli Mamadou Lamine Tall Damien Salmon Diane Laleye Carole Dhelens Elhadji Diouf Christine Pivot Fabrice Pirot |
| author_sort | Samira Filali |
| collection | DOAJ |
| description | A new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens (0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to (i) prepare low-dose melatonin hard capsules for pediatric use controlled by two complementary methods and (ii) carry out a stability study in order to determine a use-by-date. Validation of preparation process was claimed as ascertained by mass uniformity of hard capsules. Multicomponent analysis by attenuated total reflectance Fourier transformed infrared (ATR-FTIR) of melatonin/microcrystalline cellulose mixture allowed to identify and quantify relative content of active pharmaceutical ingredients and excipients. Absolute melatonin content analysis by high performance liquid chromatography in 0.5 mg and 6 mg melatonin capsules was 93.6%±4.1% and 98.7%±6.9% of theoretical value, respectively. Forced degradation study showed a good separation of melatonin and its degradation products. The capability of the method was 15, confirming a risk of false negative <0.01%. Stability test and dissolution test were compliant over 18 months of storage with European Pharmacopoeia. Preparation of melatonin hard capsules was completed manually and melatonin in hard capsules was stable for 18 months, in spite of low doses of active ingredient. ATR-FTIR offers a real alternative to HPLC for quality control of high-dose melatonin hard capsules before the release of clinical batches. |
| first_indexed | 2024-12-14T09:32:36Z |
| format | Article |
| id | doaj.art-98cd61836c8044448401843d4126a98a |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-14T09:32:36Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-98cd61836c8044448401843d4126a98a2022-12-21T23:08:02ZengElsevierJournal of Pharmaceutical Analysis2095-17792017-08-017423724310.1016/j.jpha.2017.04.001Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trialSamira Filali0Charlotte Bergamelli1Mamadou Lamine Tall2Damien Salmon3Diane Laleye4Carole Dhelens5Elhadji Diouf6Christine Pivot7Fabrice Pirot8Service pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceService pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d′Arsonval, F-69437 Lyon Cedex 03, FranceA new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens (0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to (i) prepare low-dose melatonin hard capsules for pediatric use controlled by two complementary methods and (ii) carry out a stability study in order to determine a use-by-date. Validation of preparation process was claimed as ascertained by mass uniformity of hard capsules. Multicomponent analysis by attenuated total reflectance Fourier transformed infrared (ATR-FTIR) of melatonin/microcrystalline cellulose mixture allowed to identify and quantify relative content of active pharmaceutical ingredients and excipients. Absolute melatonin content analysis by high performance liquid chromatography in 0.5 mg and 6 mg melatonin capsules was 93.6%±4.1% and 98.7%±6.9% of theoretical value, respectively. Forced degradation study showed a good separation of melatonin and its degradation products. The capability of the method was 15, confirming a risk of false negative <0.01%. Stability test and dissolution test were compliant over 18 months of storage with European Pharmacopoeia. Preparation of melatonin hard capsules was completed manually and melatonin in hard capsules was stable for 18 months, in spite of low doses of active ingredient. ATR-FTIR offers a real alternative to HPLC for quality control of high-dose melatonin hard capsules before the release of clinical batches.http://www.sciencedirect.com/science/article/pii/S2095177917300461MelatoninStability-indicating methodHigh-performance liquid chromatographyMulticomponent infrared analysisClinical trialAutism |
| spellingShingle | Samira Filali Charlotte Bergamelli Mamadou Lamine Tall Damien Salmon Diane Laleye Carole Dhelens Elhadji Diouf Christine Pivot Fabrice Pirot Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial Journal of Pharmaceutical Analysis Melatonin Stability-indicating method High-performance liquid chromatography Multicomponent infrared analysis Clinical trial Autism |
| title | Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial |
| title_full | Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial |
| title_fullStr | Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial |
| title_full_unstemmed | Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial |
| title_short | Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial |
| title_sort | formulation stability testing and analytical characterization of melatonin based preparation for clinical trial |
| topic | Melatonin Stability-indicating method High-performance liquid chromatography Multicomponent infrared analysis Clinical trial Autism |
| url | http://www.sciencedirect.com/science/article/pii/S2095177917300461 |
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