Development of Duloxetine Hydrochloride Tablets for Delayed and Complete Release Using Eudragit L 100

The purpose of the research was to optimize the preparation of duloxetine hydrochloride (duloxetine HCl) delayed release tablets. Duloxetine HCl produces a toxic substance called alpha-naphthol when duloxetine HCl is in contact with gastric fluid. Thus, duloxetine HCl when given orally needed a protective enteric coating that disable the delivery of duloxetine HCl in gastric fluid while enabling the drug delivery only in small intestine. Four different core tablets were prepared by direct compression technique, and the one which displayed quick disintegration and dissolution was chosen for enteric coating. The compressed tablets were enteric coated by dip coating technique. Since subcoating is required to safeguard the enteric coating, the core tablets were subcoated by using polymer HPMC K15M and then enteric coated with Eudragit L 100. The prepared tablets were assessed for the entire precompression and postcompression characteristics. FTIR study revealed the existence of all prominent peaks signifying its compatibility and authenticity. The in vitro studies showed that enteric-coated tablets were capable of restricting release in acidic media. The formulation F8 was optimised with 5% and 15% increase in weight of seal coat and enteric coat with good dissolution profile. Stability studies revealed that the optimized formulation was intact without any deterioration for 3 months. In conclusion, the optimized formulation could resist the drug release in acidic environment of gastrointestinal region and release the drug at a time once the tablet reaches the intestine.

Case report: narcolepsy type 2 due to the optic nerve infection of Herpes zoster virus

Rationale: Despite the acknowledged importance of environmental risk factors in the etiology of narcolepsy, there is little research on this topic. The optic nerve infection of Herpes zoster virus as a trigger for narcolepsy has not been investigated.Patient concerns: A 63-year-old male carpenter complained of excessive daytime sleepiness (EDS) over the past 3 years.Interventions: Treated with duloxetine hydrochloride enteric dissolution capsule (Cymbalta) 120mg after breakfast and clonazepam tablets 0.5mg before sleep.Outcomes: General examination showed no abnormalities of his heart, lungs, or abdomen. Neurological examination showed no positive sign. The blood routine and biochemical examination were normal. Denied having been vaccinated against the flu or having been infected with the flu virus. He scored 17 on the Pittsburg sleep quality index, 22 on the Epworth sleepiness scale, 40 on the self-rating anxiety scale, and 69 on the self-rating depression scale. The multiple sleep latency test data showed 2 periods of sleep-onset rapid eyes movement period across 4 successive tests; the average sleep latency was 7.9 minutes, and the rapid eyes movement latency was 1.2 minutes. Treated with duloxetine hydrochloride enteric dissolution capsule (Cymbalta) 120mg after breakfast and clonazepam tablets 0.5mg before sleep, the patient’s EDS symptoms disappeared immediately. He scored 6 on the Epworth sleepiness scale. During our follow-up three months later, he remained well with no complications.Diagnosis: We diagnosed the patient with narcolepsy type 2 according to the 3rd Edition of International Classification of Sleep Disorders (ICSD-3).Conclusion: The patient suffered from EDS and was diagnosed with narcolepsy type 2. The narcolepsy type 2 was linked to viral infection of the optic nerve. Optic nerve virus infection may affect the sleep-pondering pathway.

A Comparative Chemometric Study for Quantitative Determination of Duloxetine Hydrochloride in the Presence of its Toxic Impurity 1-Naphthol

Background: Duloxetine hydrochloride (DUL) is a serotonin-norepinephrine reuptake inhibitor. It is used for treating depression and anxiety. It is available in the market as a capsule called Cymbatex®, which is used for the treatment of depression. 1-naphthol is a potential impurity of DUL. It is hepatotoxic to humans and has potential toxicity to freshwater fish. Objective: Duloxetine hydrochloride was determined in the presence of its toxic impurity 1-naphthol in raw material and in pharmaceutical dosage forms using three multivariate calibration chemometric methods. Methods: Classical Least Squares (CLS), Partial Least-Squares (PLS) and linear support vector regression (SVR) were developed using UV spectral data. The three methods were compared among each other and the advantages and disadvantages were discussed. For good results, a two-factor four-level experimental design was used, resulting in a training set of 16 mixtures containing different ratios of each component. The test set consisting of nine mixtures was necessary to test the ability of the proposed methods to predict DUL in the presence of its impurity, 1-naphthol. Results: The results show the success of the three developed methods to determine DUL in the presence of small levels of its toxic impurity with good accuracy and selectivity. The results of the dosage form were compared statistically to that of the reported HPLC method, with no significant difference in accuracy and precision. Conclusion: The suggested calibration models are suitable for routine analysis of the drug in bulk and pharmaceutical dosage forms. Compared to the CLS and PLS models, the SVR model gives the best results regarding the accuracy with a lower prediction error and better generalization ability. However, the CLS and PLS models are found to be simpler and faster in usage and management.