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Pharmacokinetics of a subcutaneous meloxicam in an extended-release (XR) gel formulation in rats

Akkaraju, Harshita (2023) Pharmacokinetics of a subcutaneous meloxicam in an extended-release (XR) gel formulation in rats. Master's Thesis, University of Pittsburgh. (Unpublished)

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For patients who undergo invasive surgeries, opioids are the most frequently recommended medications for the management of moderate to severe pain. Opioid dependence and illicit usage have increased significantly because of the high prevalence of this practice. Despite efforts made to address this public health epidemic, opioid overdose-related mortality has been on the rise for many years. Therefore, finding comparable alternatives to opioid-based pain therapy is urgently needed.

The effectiveness of NSAIDs for opioid-free pain treatment has been the subject of numerous studies. Meloxicam, a cyclooxygenase 2 (COX-2) selective NSAID, is recommended for the treatment of diseases such as rheumatoid arthritis and osteoarthritis. Through the specific COX-2 inhibition, meloxicam reduces pain and exhibits an improved gastrointestinal (GI) safety profile in comparison to non-selective NSAIDs.

Meloxicam XR gel, a depot formulation intended for subcutaneous administration was developed in Dr Rohan’s lab at the University of Pittsburgh, PA. We anticipate that meloxicam XR gel will provide an extended release over a long period of time. This will help the analgesic effects to last longer, requiring less frequent dosing.
We developed and validated a HPLC assay method to detect and quantify meloxicam and its metabolites – hydroxy meloxicam and carboxy meloxicam in rat plasma using a Waters Alliance e2695 Separations Module at a wavelength of 360 nm. The system was equipped with a Waters 2489 UV/Visible Detector and a Xbridge C18 column (50 mm length) which was used to achieve chemical separation at 35 °C. The mobile phase consisted of a 75:25 potassium phosphate (50mM, pH: 2.15) and acetonitrile (ACN), pumped at a flow rate of 1.0 mL/min.

A study was performed to evaluate the pharmacokinetics by assessing the drug concentrations in plasma over time when meloxicam XR gel was administered subcutaneously to male sprague dawley rats. The novel XR formulation was also compared to meloxicam given by solution – intravenous (IV), subcutaneous (SC) and a sustained release (SR) formulation marketed by Zoopharm LLC. Blood samples were collected from 20 male rats at specific time points after solution (IV, SC) and SC gel formulation injections and plasma was separated by centrifugation. Plasma samples were assayed by HPLC method described above. Non compartment analysis (NCA) was performed to estimate various plasma pharmacokinetic parameters.

We observed that XR gel’s plasma levels are above the minimum effective concentration (MEC) for a longer duration as compared to the solution (IV, SC). We conclude that the plasma meloxicam concentration was maintained above the MEC for about 96 hours after the subcutaneous administration of the XR gel formulation, showing that the XR gel can be administered less frequently compared to the IV or SC administration of the solution.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Akkaraju, Harshitaharshuakkaraju@gmail.comhaa144@pitt.edu0000-0001-8131-0104
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorVenkataramanan,
Thesis AdvisorShaik,
Committee MemberRohan,
Date: 3 May 2023
Date Type: Publication
Defense Date: 6 April 2023
Approval Date: 3 May 2023
Submission Date: 17 April 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 65
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Pharmacokinetics, Meloxicam, XR gel, subcutaneous, rats
Date Deposited: 03 May 2023 13:45
Last Modified: 03 May 2023 13:45


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