Project Title

Rapidly Dissolving Polymeric Microneedle Skin Patch of Naloxone for Opioid Overdose Treatment

Authors' Affiliations

Akeemat O. Tijani, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Maria J. Pelaez, Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA. Prashant Dogra, Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA. Ashana Puri, East Tennessee State University.

Location

Culp Ballroom

Start Date

4-7-2022 9:00 AM

End Date

4-7-2022 12:00 PM

Poster Number

34

Faculty Sponsor’s Department

Pharmaceutical Sciences

Name of Project's Faculty Sponsor

Ashana Puri

Classification of First Author

Graduate Student-Doctoral

Competition Type

Competitive

Type

Poster Presentation

Project's Category

Behavioral Problems or Disorders, Chronic Illnesses, Mental Disorders, Public Health

Abstract or Artist's Statement

Rapidly Dissolving Polymeric Microneedle Skin Patch of Naloxone for Opioid Overdose Treatment

Tijani Akeemat1, Maria J. Peláez2, Prashant Dogra2,3, Ashana Puri1

1 Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614.

2 Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA

3 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA

Worldwide opioid abuse affects over 16 million people. A major cause of death in abusers is overdosing. Naloxone (NAL) is an opioid inhibitor that reverses its respiratory depressing effect. The use of this drug is limited mostly to invasive delivery: intravenous (IV), intramuscular (IM) and subcutaneous (SC) due to its significant hepatic clearance and poor oral bioavailability (2%). These routes are painful and worse still is the need for frequent injections for patient stabilization due to the short half-life of NAL. Non-invasive intranasal forms exist but this is fraught with a couple of limitations such as nasal damage and epistaxis. The need for alternatives without these limitations is thus evident. The feasibility of the use of metal microneedles (MNs) for the transdermal delivery of NAL was demonstrated in-vitro and through in-vitro in-vivo correlation modeling in our lab. The goal of the current study was to design a rapidly dissolving polymeric MN patch with delivery and pharmacokinetic (PK) properties comparable to that seen with the commercially available NAL products, eliminating their highlighted limitations. NAL loaded rapidly dissolving polyvinyl pyrrolidone-based MN arrays (500 µm, 100 needles) were fabricated by the mold casting technique. The permeation profile of fabricated MNs over a predetermined time were assessed via an in-vitro permeation set up using porcine ear skin. Samples were analyzed via HPLC. To improve on drug flux and amount permeated, the effect of increasing MN length and density (no. of needles/unit area) were assessed by fabricating MNs 300 µm longer and those with density double that of the initial array. Factors such as drug load and polymer strength influenced the needle fabrication. Compared to passive permeation, a reduced lag time of about 15 min was observed with a significant drug flux of 15.09 ± 7.68 g/cm2/h seen in the first 1 h (pin-vitro in-vivocorrelation we were able to predict an optimized design of the patch that can reproduce the clinical PK of NAL obtained with commercial devices. Increasing needle density and/or patch area was found to be of greater significance. Overall, drug flux seen over 1 h depicts the applicability of fabricated needles in opioid overdose emergencies with delivery properties comparable to that with IM and IN delivery.

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Apr 7th, 9:00 AM Apr 7th, 12:00 PM

Rapidly Dissolving Polymeric Microneedle Skin Patch of Naloxone for Opioid Overdose Treatment

Culp Ballroom

Rapidly Dissolving Polymeric Microneedle Skin Patch of Naloxone for Opioid Overdose Treatment

Tijani Akeemat1, Maria J. Peláez2, Prashant Dogra2,3, Ashana Puri1

1 Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614.

2 Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA

3 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA

Worldwide opioid abuse affects over 16 million people. A major cause of death in abusers is overdosing. Naloxone (NAL) is an opioid inhibitor that reverses its respiratory depressing effect. The use of this drug is limited mostly to invasive delivery: intravenous (IV), intramuscular (IM) and subcutaneous (SC) due to its significant hepatic clearance and poor oral bioavailability (2%). These routes are painful and worse still is the need for frequent injections for patient stabilization due to the short half-life of NAL. Non-invasive intranasal forms exist but this is fraught with a couple of limitations such as nasal damage and epistaxis. The need for alternatives without these limitations is thus evident. The feasibility of the use of metal microneedles (MNs) for the transdermal delivery of NAL was demonstrated in-vitro and through in-vitro in-vivo correlation modeling in our lab. The goal of the current study was to design a rapidly dissolving polymeric MN patch with delivery and pharmacokinetic (PK) properties comparable to that seen with the commercially available NAL products, eliminating their highlighted limitations. NAL loaded rapidly dissolving polyvinyl pyrrolidone-based MN arrays (500 µm, 100 needles) were fabricated by the mold casting technique. The permeation profile of fabricated MNs over a predetermined time were assessed via an in-vitro permeation set up using porcine ear skin. Samples were analyzed via HPLC. To improve on drug flux and amount permeated, the effect of increasing MN length and density (no. of needles/unit area) were assessed by fabricating MNs 300 µm longer and those with density double that of the initial array. Factors such as drug load and polymer strength influenced the needle fabrication. Compared to passive permeation, a reduced lag time of about 15 min was observed with a significant drug flux of 15.09 ± 7.68 g/cm2/h seen in the first 1 h (pin-vitro in-vivocorrelation we were able to predict an optimized design of the patch that can reproduce the clinical PK of NAL obtained with commercial devices. Increasing needle density and/or patch area was found to be of greater significance. Overall, drug flux seen over 1 h depicts the applicability of fabricated needles in opioid overdose emergencies with delivery properties comparable to that with IM and IN delivery.