Pharma-engineering of multifunctional microneedle array device for application in chronic pain

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within this thesis is the possibility of further developing transdermal drug delivery for chronic pain treatment using an Electro-Modulated Hydrogel- Microneedle array (EMHM) prototype device for the delivery of analgesic medicatio

In vivo evaluation of an Ultra-fast Disintegrating Wafer matrix : a molecular simulation approach to the ora-mucoadhesivity

The purpose of this study was to design and evaluate the performance of an Ultra-fast Disintegrating Wafer (U-D-WAF) loaded with highly water soluble diphenhydramine hydrochloride (DPH) through the oramucosa of the Large White Pig model. For the first time this work explored the oramucosivity of the U-D-WAF by detailed molecular modeling of the matrix on buccal tissue in order to mechanistically deduce the mucodhesivity. The U-D-WAF was formulated using a blend of hydroxypropylcellulose, poly(acrylic) acid, sodium starch glycolate and β –cyclodextrin in accordance with a Box-Benkhen experimental design for optimization prior to ex vivo permeation and in vivo release studies in the Large White Pig. Molecular simulation studies assess the mucoadhesivity of the U-D-WAF to the oramucosa. A mean Drug Entrapment Efficiency of 72.96 ± 4.32%, disintegration time of 29.33 ± 15.91 s and drug release after 60 s of 86.32 ± 20.37% was recorded. Ex vivo permeation studies revealed cumulative drug permeation of 86.32 ± 20.34% 60 s after onset. In vivo evaluation of the optimized U-D-WAF had a Cmax = 59 μgL−1 approximately 300 s after administration. The ultrafast disintegration of the U-D-WAF matrix with desirable mucoadhesivity in in vitro and in vivo studies makes it suitable for effective and rapid oramucosal drug delivery.The National Research Foundation (NRF) and the Technology Innovation Agency (TIA) of South Africa.http://www.elsevier.com/locate/jddst2018-02-20hj2018Paraclinical Science

3D Printed, PVA–PAA Hydrogel Loaded-Polycaprolactone Scaffold for the Delivery of Hydrophilic In-Situ Formed Sodium Indomethacin

3D printed polycaprolactone (PCL)-blended scaffolds have been designed, prepared, and evaluated in vitro in this study prior to the incorporation of a polyvinyl alcohol–polyacrylic acid (PVA–PAA) hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL–PVA–PAA scaffold is proposed as a potential structural support system for load-bearing tissue damage where inflammation is prevalent. Uniaxial strain testing of the PCL-blended scaffolds were undertaken to determine the scaffold’s resistance to strain in addition to its thermal, structural, and porosimetric properties. The viscoelastic properties of the incorporated PVA–PAA hydrogel has also been determined, as well as the drug release profile of the PCL–PVA–PAA scaffold. Results of these analyses noted the structural strength, thermal stability, and porosimetric properties of the scaffold, as well as the ability of the PCL–PVA–PAA scaffold to deliver sodium indomethacin in simulated physiological conditions of pH and temperature. The results of this study therefore highlight the successful design, fabrication, and in vitro evaluation of a 3D printed polymeric strain-resistant supportive platform for the delivery of sodium indomethacin

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles. This review encompasses the strategies and techniques that have been utilized to target the HBV-infected nuclei in liver hepatocytes, with a significant look at the new insights and most recent advances in drug carriers and their role in anti-HBV therapy

Current advances in the fabrication of microneedles for transdermal delivery

The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds as desired. The use of hypodermic needles, associated with phobia, pain and accidental needle-sticks has been used to overcome the delivery limitation of macromolecular compounds. The means to overcome the disadvantages of hypodermic needles has led to the development of microneedles for transdermal delivery. However, since the initial stages of microneedle fabrication, recent research has been conducted integrating various fabrication techniques for generating sophisticated microneedle devices for transdermal delivery including progress on their commercialization. A concerted effort has been made within this review to highlight the current advances of microneedles, and to provide an update of pharmaceutical research in the field of microneedle-assisted transdermal drug delivery system

In vitro and in vivo evaluation of an oral multi-layered multi-disk tablet for specialized chronotherapeutic drug delivery

Chronotherapeutic disorders such as hypertension, cardiovascular disease and asthma commonly involve the use of controlled zero-order release formulations. Ideally, the required drug should be released at predetermined rates with two or more pulses released from the dosage form. This ultimately exposes the patient to drug only when required, reducing the number of dosages, reducing side-effects and increasing patient compliance. The aim of this research was to evaluate two Multi-Layered Multi-Disk Tablet (MLMDT) systems incorporating drug-loaded disks enveloped by three polymeric layers. The model drugs used for each system were theophylline and diltiazem hydrochloride. The proposed chronotherapeutic system was designed to provide a lag phase and then two pulses of drug release separated by a ‘switch-off’ phase. In vitro drug release analysis revealed that the MLMDT generated a lag phase or a ‘switch-off’ phase followed by two pulses of drug release over the evaluated 24 h period. In vivo testing was undertaken using a Large White Pig Model, where concentration analysis from the evaluated conventional products revealed increasing plasma concentrations up to 2 h followed by a steady decline in concentration while the developed MLMDT displayed two pulse prolonged drug release profile separated by a switch-off phase.The National Research Foundation (NRF) of South Africa.http://www.elsevier.com/locate/jddst2019-06-01hj2019Paraclinical Science