Abstract
Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis.
Highlights
Chronotherapeutics refers to a treatment method that is in accordance with a patient’s daily, monthly, seasonal or yearly biological clock, in order to achieve maximum therapeutic benefits and minimal adverse effects
Chronotherapeutic drug delivery systems (ChrDDs) with a preset lag time are helpful for patients suffering from allergic rhinitis, rheumatoid arthritis (RA) and related disorders, asthma, cancer, cardiovascular diseases and peptic ulcer disease as the drug is released at a predetermined time and the maximum concentration (Cmax) of the drug will be reached when the symptoms of the disease are at its peak [1,2,3]
The primary goal for developing any dosage form is to deliver the required concentration of an active drug substance to the site of action and to achieve optimum efficacy
Summary
Chronotherapeutics refers to a treatment method that is in accordance with a patient’s daily, monthly, seasonal or yearly biological clock, in order to achieve maximum therapeutic benefits and minimal adverse effects. Chronotherapeutic drug delivery systems (ChrDDs) with a preset lag time are helpful for patients suffering from allergic rhinitis, rheumatoid arthritis (RA) and related disorders, asthma, cancer, cardiovascular diseases and peptic ulcer disease as the drug is released at a predetermined time and the maximum concentration (Cmax) of the drug will be reached when the symptoms of the disease are at its peak [1,2,3]. Chronopharmacotherapy for RA has been recommended to ensure that the highest blood levels of the drug coincide with the incidence of pain and stiffness. The outer layer disintegrates or dissolves slowly to release the drug after a predetermined lag time [5, 6]
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