Insertion of Dual Drugs of Hypertension in Gelatin Pockets for Chrono pharmacotherapy and its Evaluation by in-vitro and ex- vivo Studies

Abstract

Objective: The project was aimed to fabricate and evaluate a pulsatile capsule to program the release of dual antihypertensive drugs to mimic the circadian pattern of Blood Pressure. The formulation was optimized to repeatedly release the drug in pulses during the vulnerable period of 4 a.m. to noon upon administration during bed time. Methods: Formulation was prepared by means of Pulsincap technology. It consisted of an insoluble capsule body housing a layer of swellable polymer, a Losartan tablet sealed by an erodible polymer tablet. The system was capsulated in non-biodegradable body capped with water soluble cap containing fast releasing Amlodipine-sorbitol granules. The developed formulation was studied for physical characteristics, lag time determination, in vitro and ex vivo release. Results: The capsule cap dissolved in acidic pH released 99.29% of the amlodipine within 3h. The swellable polymer layer at the base of capsule pushed the plug along with losartan tablet out after a lag time of 6-7 h with 85.93% drug being released at the end of 12 h providing a time controlled need based release. Pulsincap formulated with Amlodipine-Sorbitol granules of G3 formulation, Losartan core tablet of C4 formulation and Erodible tablet of Guar gum with E4 formulation showed highest drug release over the period of 12 h and release was found to be followed Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of dual drugs is a suitable device for the time dependent and site specific delivery. Conclusion: This approach can be useful for the timed release of a combination antihypertensive medication and may provide effective 24 h control of Blood Pressure in hypertensive patients. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.

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“…Drug-excipient compatibility was studied by utilizing ATR-FTIR spectroscopy [17] (PerkinElmer). The FTIR overlay of rosuvastatin calcium and SEDDS formulation (F6), samples were scanned for IR spectra from 4000 to 400 cm −1 .…”

A Rapid HPLC Method for the Concurrent Determination of Several Antihypertensive Drugs from Binary and Ternary Formulations

“…Telmisartan, olmesartan, and irbesartan are available on the market in combination with amlodipine and hydrochlorothiazide (Figure 1), manufactured by the same or different pharmaceutical industries [4]. Different analytical methods such as spectrophotometric [11][12][13][14][15][16][17][18], derivative spectrofluorimetric [19], HPLC [20][21][22][23][24][25][26][27], electrophoresis [28], and HPTLC [29] were reported for the concurrent determination of sartans, amlodipine, or hydrochlorothiazide from formulations and biological fluids. The literature has also reported a few analytical methods for the concurrent determination of ternary mixtures of sartans, amlodipine, and hydrochlorothiazide [30][31][32][33][34].…”

Development of UV Spectrophotometric Procedures for Determination of Amlodipine and Celecoxib in Formulation: Use of Scaling Factor to Improve the Sensitivity

“…ese analytical methods include spectrophotometric methods [7][8][9], spectrofluorometric methods [10], HPTLC [11], RP-HPLC [12][13][14], LCMS/MS [15], capillary electrophoresis, and electrochemical methods [16][17][18][19][20][21][22][23]. Celecoxib, (COX) selective cox-2 inhibitor, is a potent analgesic, antipyretic, and anti-inflammatory drug.…”