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European Journal of Pharmaceutical... Jan 2024This study aimed to develop a dissolution test that can predict the bioequivalence (BE) of enteric-coated pellet formulations. The original duloxetine hydrochloride...
This study aimed to develop a dissolution test that can predict the bioequivalence (BE) of enteric-coated pellet formulations. The original duloxetine hydrochloride capsule (reference formulation (RF); Cymbalta® 30 mg capsule) and four generic test formulations (two capsules (CP) and two orally disintegrating tablets (OD)) were used as model formulations. Clinical BE studies were conducted on 24-47 healthy male subjects under fasting conditions. Dissolution tests were performed using a compendial paddle method (PD) (paddle speed: 50 rpm) and a flow-through cell method (FTC) (flow rate: 4 mL/min). For a further test, cotton balls were added to the vessel to apply gentle mechanistic stress to the formulations, and paddle speed was reduced to 10 rpm (paddle with cotton ball method (PDCB)).All the dissolution tests were conducted with 0.01 M HCl (pH 2.0) for 0.5 h followed by 10 mM bicarbonate buffer solutions (pH 6.5) for 4 h. One each of the two CP and two OD showed BE with RF. PDCB was able to discriminate between BE and non-BE formulations, while this was not possible with PD and FTC. In PDCB, the cotton balls intermittently moved the pellets near the vessel bottom. PDCB is useful for predicting BE during formulation development.
Topics: Male; Humans; Bicarbonates; Therapeutic Equivalency; Tablets, Enteric-Coated; Tablets; Duloxetine Hydrochloride; Solubility
PubMed: 37884100
DOI: 10.1016/j.ejps.2023.106622 -
Scientific Reports May 2024Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence... (Randomized Controlled Trial)
Randomized Controlled Trial
Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.
Topics: Humans; Fibromyalgia; Hyperbaric Oxygenation; Female; Male; Adult; Middle Aged; Child Abuse, Sexual; Prospective Studies; Duloxetine Hydrochloride; Pregabalin; Treatment Outcome; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Analgesics
PubMed: 38773296
DOI: 10.1038/s41598-024-62161-5