Formulation, stability testing, and analytical characterization of melatonin-based preparation for clinical trial

Abstract

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.

Application of a New Validated HPLC-PDA Method for Simultaneous Determination of Curcumin and Melatonin in Hyaluronic Acid-Coated Nanoemulsions

“…3.2). 46,47 The purity of the peaks was confirmed by the comparison of spectra recorded with PDA detector during the registration of chromatographic profile. 48 The λmax values were determined by scanning with PDA detector from 200 to 500 nm; the maximum light absorption for CUR and MEL occurred at 425 and 223 nm, respectively, and these wavelengths were chosen to quantify the drugs in the nanoemulsions.…”

Formulation and evaluation of the topical ethosomal gel of melatonin to prevent UV radiation

“…Then LOQ was measured by using mathematical expressions given in section. The limit of quantification (LOQ) of the drug was calculated by using the following equations designated by International Conference on Harmonization (ICH) guideline:Where, σ = the standard deviation of the response, S = slope of the calibration curve …”

Measurement, analysis and prediction of amoxicillin oral dose stability from integrated molecular description approach and accelerated predictive stability (APS)

“…ATR-FTIR spectrum of individual components (AS, ATH and MCC) was recorded by a diamond crystal containing a standard deuterated triglycine sulfate detector (10-cm optical path, 32 scans with spectral resolution of 4 cm −1 ). The spectra were compared to amoxicillin mixture and amoxicillin pharmacopeia standard [10]. Omnic Spectra® software was used to analyze individual and multi-component spectra.…”

“…Degradation rate models A and B, detailed in Table 4, were fitted by using the statistical computing and graphic software "R" [14]. Models were evaluated through the Bayesian Information Criterion (BIC), Akaike Information Criterion (AIC) and the Relative Mean Square Error (RMSE) [6][7][8][9][10][11][12][13][14][15]. Finally, the best fitted model was used to predict the long-term degradation rate of amoxicillin over 24 months in the common ICH environmental conditions (25°C / 60% RH, 30°C / 65% RH and 40°C / 75% RH).…”