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Background: Kalyanaka Ghrita (KG) is polyherbal oleaginous medicament consisting of extracts from twenty-eight different plants, indicated for management of psychosomatic disorders like Unmada (Schizophrenia), Apasmara (Epilepsy) and numerous other ailments., Objective: To develop and validate standard manufacturing procedure of KG by following Ayurvedic principles in three batches to ensure process uniformity and standards., Materials and Methods: Three batches of KG were prepared by adopting principles of Ashtanga Hrudya and Ayurvedic Formulary of India to ensure consistency in manufacturing process. Observations during process such as temperature, duration were recorded. KG was subjected to chief desired characteristics, organoleptic (color, odour, taste, texture, touch), physicochemical (acid value, peroxide value, iodine value, saponification value, loss on drying, refractive index, specific gravity, mineral oil, rancidity test, viscosity) as per pharmacopeial standard. Chromatographic screening and fingerprinting of KG were conducted through GCMS whereas quantification of curcumin and chebulagic acid biomarkers were assessed through HPLC., Results: Average yield of KG was 83.41%, with average intermittent heating duration of 20.35 h subsequently divided into three days. Temperature throughout preparation ranged from 66 °C to 101 °C. KG was pale olive in colour, exhibiting pleasant taste, characteristic smell, and soft texture. Organoleptic and physicochemical characters were comparable for three batches of KG while safety parameters were found within permissible limits., Conclusion: Pharmaceutical standardization of Kalyanaka Ghrita is necessary for establishing biological and chemical profile of formulations. Present study recommends use of coarse powdered ingredients for optimal yield during pharmaceutical process, and heating up to Madhyama Paka stage calibrated over three days with average temperature of 85 °C. The data obtained from this study may contribute to future research and development activities, serving as a basis for manufacturing standards of KG., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NONE., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The effect of pretreatment with graded concentration of diltiazem on the inotropic responses to amrinone were studied on isolated atria of rabbit. The responses to amrinone were modified by diltiazem in a biphasic manner; initial potentiation followed by inhibition. The potentiation is proposed to be due to synergistic rise in cytosolic calcium ion concentration by diltiazem and amrinone. The inhibition by diltiazem in higher concentration may be due to blockade of calcium ion influx and depletion of intracellular calcium ion from storage sites.

In a double blind short term clinical study, nitroxazepine has been found to be superior over placebo in reducing the diastolic blood pressure in mild hypertensive patients. In short term open clinical trial design nitroxazepine (25 mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg PO, HS). In open clinical trial design, nitroxazepine (25 mg PO, HS) reduced the diastolic blood pressure to the target level (100 mm Hg and less) effectively controlling the uncontrolled hypertensive patients receiving maintenance dose of beta blockers. There was no such beneficial effect in patients receiving maintenance doses of other antihypertensive drugs (pilot study). Adverse drug reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and dryness of mouth in one patient have been observed.

Diltiazem, a calcium channel blocker was studied to observe its effects on the acetylcholine contractile responses of isolated frog rectus abdominis muscle. This response was modified in a dual manner i.e., initial potentiation, followed by inhibition. Diltiazem may not have anticholinesterase like mechanism, as it potentiated the responses to both acetylcholine and succinylcholine. Rectus muscle preparation, incubated in calcium free frog Ringer, showed dose dependent inhibition of acetylcholine contractile responses by diltiazem. The study suggests that diltiazem inhibits calcium ion influx across receptor operated calcium channels and may also inhibit calcium ion release from intracellular structures.