Formulation and evaluation of dexlansoprazole extended-release tablet

Dexlansoprazole (DSP) is a proton pump inhibitor, it used to treat GERD and ulcer colitis. DSP works by decreasing the volume of acid in the stomach. DSP is an acid-labile medication that may be destroyed in the stomach's acidic pH. A coating technique was used to postpone drug release in the stomach, which can extend pharmacological activity. Shellac can be used to develop the sustain release tablet of dexlansoprazole as retardation of the drug (dexlansoprazole) was observed in the acidic pH of the stomach, and hence a sustain coated dexlansoprazole tablet was prepared and evaluated. The coating's primary function is to allow for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits faster degradation in the acidic pH of the stomach, therefore increasing pharmacological action. DSP coating with different polymers inhibits fast degradation in the stomach's acidic pH, enhancing pharmacological action. The major function of the coating is to enable for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits fast breakdown in the stomach's acidic pH, enhancing pharmacological action.

Neuroleptic Malignant Syndrome in an Elderly Patient with Bipolar Disorder

Neuroleptic malignant syndrome (NMS) is a well-known and potentially fatal complication of antipsychotic use. The elderly population, with multiple risk factors, are more vulnerable to this condition. We described a case of an 80-yearold man with bipolar disorder, previously on oral extended-release sodium valproate, aripiprazole and long-acting injectable paliperidone, who developed NMS. He presented with generalised muscle rigidity, fever, fluctuating blood pressure and elevated creatinine kinase during his hospitalisation for a manic episode. Contributing factors included old age, underlying vascular Parkinsonism, electrolyte imbalance, intercurrent lung infection with acute exacerbation of chronic obstructive pulmonary disease, hyperactive delirium, and repeated administration of parenteral typical antipsychotic. Antipsychotics were withheld promptly, and the patient was treated with dantrolene, bromocriptine and amantadine. His symptoms resolved after a week. He subsequently remained well with oral extended-release sodium valproate alone. Relevant clinical points are discussed. Clinical vigilance, close interdisciplinary cooperation, and prompt interventions are keys to successful to management of NMS in elderly patients.

A Prospective, Multicenter, Open-Label Study of The Clinical Efficacy of Tapentadol Extended-Release in The Treatment of Cancer-Related Pain and Improvement of Quality of Life in Opioid-Naïve or Opioid-Resistant Patients

Purpose: This study was to investigate the clinical efficacy of tapentadol extended-release (ER) on pain control and the quality of life of patients with moderate to severe chronic cancer pain in clinical practice in Korea.Methods: In this prospective, open-label, multicenter trial, patients with sustained cancer pain as well as chronic pain, using or not using other analgesics were enrolled. Thirteen centers recorded a total of 752 patients, during the 6-month observation period, based on the tapentadol ER dose and tolerability, prior and concomitant analgesic treatment, pain intensity, type of pain, adverse effects, and clinical global impression change (CGI-C). A total of 752 patients were screened, 688 were enrolled, and 650 completed the study for efficacy and adverse drug reactions; among them 349 were cancer patients.Results: In total, 752 patients were screened, 688 were enrolled and 650 were completed the study for efficacy and adverse drug reactions, 349 of whom were cancer patients. Tapentadol ER significantly reduced the mean pain intensity including neuropathic pain during the observation period by 2.9 points (from a mean 7±0.87 to 4.1±2.02). Furthermore, the quality of life was observed to be significantly improved based on an objective observation, such as the CGI-C.Conclusion: This study showed that tapentadol ER was effective in patients with moderate to severe cancer pain and was also effective in neuropathic pain, and therefore it significantly improved the patients’ quality of life.

Comparison of Hydroxypropylcellulose and Hot-Melt Extrudable Hypromellose in Twin-Screw Melt Granulation of Metformin Hydrochloride: Effect of Rheological Properties of Polymer on Melt Granulation and Granule Properties

High-molecular-weight hypromellose (HPMC) and hydroxypropyl cellulose (HPC) are widely known, extended-release polymers. Conventional high-molecular-weight HPMCs are preferred in extended-release applications but not widely used in twin-screw melt granulation due to processability difficulties at low operating temperatures and potential drug degradation if high processing temperatures are used. Conversely, high-molecular-weight grade HPC (Klucel®) can be used in melt granulation processes. The purpose of this study was to evaluate the processability and dissolution behavior of HPC GXF ((Klucel® GXF) and a recently introduced type of hot-melt extrudable HPMC (Affinisol®) in extended-release metformin hydrochloride formulations using twin-screw melt granulation. Powder blends were prepared with 75% w/w metformin HCl and 25% w/w polymeric binder. Blends were granulated at processing temperatures of 160, 140, 120 and 100 °C. HPMC HME 4M (Affinisol® 4M) provided a fine powder, indicating minimum granulation at processing temperatures lower than 160 °C, and the tablets obtained with these granules capped during tableting. In contrast, acceptable tablets could be obtained with HPC GXF at all processing temperatures. Rheological studies including capillary rheometry to measure steady shear rate viscosity, and rotational rheometry to obtain time and temperature superposition data, showed that HPC GXF had a greater thermoplasticity than HPMC HME 4M, which made granulation possible with HPC GXF at low temperatures. Tablets compressed with granules obtained at 160 °C with both binders showed comparable dissolution profiles. High-molecular-weight HPC GXF provided a better processability at low temperatures and adequate tablet strength for the melt granulation of metformin HCl.

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

Preclinical pharmacokinetic (pK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the pK behavior of drug and/or its dosage forms prior to clinical studies on humans and help in tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports first of its kind preclinical pK study on oral extended release (ER) solid dosage formulations of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment different types of depression disorders worldwide. The LC-MS/MS bioanalytical method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid phase extraction for sample preparation followed by an ultra-fast LC-MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

GOCOVRI® (amantadine) extended-release capsules in Parkinson's disease

Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia, in fluctuating orally levodopa treated patients. It additionally ameliorates ‘off’-intervals characterized by impaired motor behavior. These beneficial effects result from higher and more continuous brain delivery of amantadine. Future clinical research is warranted on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase on motor complications in orally levodopa treated patients, as all these pharmacological principles support the concept of continuous dopamine substitution.