International Conference and Exhibition on Pain Medicine June 08-10, 2015 Chicago, USA

Srinath Muppalaneni earned a BS in Pharmacy from Andhra University and a MS in Pharmaceutical Sciences from Campbell University. He is currently a Doctoral candidate in Pharmaceutics at Nova Southeastern University (NSU) with dissertation research focusing on abuse-deterrent formulations. He has so far participated in 6 inventions, 3 publications, 26 presentations, 1 grant, and 2 book chapters. He also won the best poster award at the 2013 OMICs 3rd International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems.

Prescription drug abuse is an epidemic, and medications that can help deter this abuse are needed. Poly (ethylene oxide) (PEO) is a common tablet excipient used in formulating abuse-deterrent medications due to its high solution viscosity and plastic-like properties after thermal treatment. This study was intended to evaluate hardness, deformation and crush resistance of both regular and heat-treated PEO tablets containing acetaminophen as a model drug. Regular tablets consisting of 80 mg acetaminophen and 320mg high molecular weight PEO (Polyox® WSR coagulant) were made on a single station Carver press, and compressed to 2000 pounds. Heat-treated tablets were further heated to 80oC for 30 minutes in a forced-convection oven. Tablet hardness and deformation were evaluated using a Vanguard hardness tester (LIH series) and a hammer, respectively. Tablet thickness and diameter were recorded before and after ten hammer strokes. Ease of crushing was determined using two manual methods, a pill crusher and a pestle-mortar, for one minute. Resultant particles were then evaluated for particle size distribution using sieve analysis. Heat-treatment increased tablet hardness from 124 ± 3.2N (n=6) to over 200 N (max reading on tester). Heat-treated tablets also deformed under hammer strokes and reduced in thickness by 16.2±0.72% (diameter increase of 7.1±0.19%) (n=3). Regular tablets were found to be easily friable and could be crushed into small particles after three strokes. Regular tablets could also be easily crushed using both the pill crusher or mortar and pestle whereas heat-treated tablets remained intact. It was concluded that thermal treatment of PEO tablets improved mechanical strength and provided plastic deformation properties.

Fereshteh Dardmeh, DVM, PhD student Fereshteh Dardmeh, graduated as a Doctor of Veterinary Medicine (D.V.M.) from Urmia University, Iran in 2011. She then joined the “Laboratory of Reproductive Biomedicine” and “Center for Sensory-Motor Interaction (SMI)” in the Department of “Health, Science and technology” of Aalborg University, Denmark as a PhD student in 2013. She has since been actively involved in teaching and research in the area of reproductive health and medicine with her current studies focusing on Probiotic supplements as a novel strategy in pain management and translational investigations of possible associations between pain, obesity and fertility. Her studies have until now resulted in several abstracts for conference presentations with full length associated articles in the pipeline.

Background and Aims: Pain thresholds or responsiveness to painful stimuli has been demonstrated to be affected by body conditions such as obesity. Generally, a lower pain threshold has been demonstrated in obesity both in animals and humans. Among the endogenous factors influencing the obesity, intestinal microbiota has also been suggested to influence the pain sensitivity. However, the effect of oral probiotics on pain has not been studied systematically. This study examined the effect of oral probiotic (Lactobacillus Rhamnusus) on mechanical sensitivity in behaving diet-induced obese (DIO) mice. Methods: Six-week old male C57BL/6NTac mice were fed with a high fat diet (week 1-4) to produce DIO mice. The DIO mice were then randomly assigned to 2 groups treated with a single daily dose (1x109 CFU) of L. Rhamnusus (test group) or physiological saline (control group) for 4 weeks (weeks 5-8). Sensitivity to mechanical stimulation (hind-paw withdrawal), was assessed by the electronic Von Frey every two weeks throughout the study period. Results: The DIO mice in the test group did not significantly gain weight after the start of probiotic administration while the control group maintained the weight rising trend leading to a significant weight difference on week 5 which remained up to week 6. The test group showed a trend of lower pain sensitivity (i.e. higher pain threshold) to mechanical stimulation compared to the control group after two weeks of receiving the probiotic treatment (12.96±0.822 g and 9.57±0.822 g, respectively, P>0.05). After 4 weeks of probiotic administration, a significant difference was observed between the two groups (16.05±0.88g in test group and 7.97±0.88g in control group; P<0.01). Conclusions: The results of this study demonstrated lower mechanical pain sensitivity in probiotic-treated obese mice. The protective effect of probiotics on nociception circuits could be associated with the weight reduction or anti-inflammatory properties of the probiotics. Translation of this result in humans can potentially suggest a novel therapeutic strategy in pain management of obese individuals.

Srinath Muppalaneni earned a BS in Pharmacy from Andhra University and a MS in Pharmaceutical Sciences from Campbell University. He is currently a Doctoral candidate in Pharmaceutics at Nova Southeastern University (NSU) with dissertation research focusing on abuse-deterrent formulations. He has so far participated in 6 inventions, 3 publications, 26 presentations, 1 grant, and 2 book chapters. He also won the best poster award at the 2013 OMICs 3rd International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems.

Opioid analgesics have high potential for abuse, and oral formulations are frequently tampered to produce greater effects. General methods of opioid tampering include crushing and solution extraction for abuse via snorting and injection, respectively. To deter crushing, poly (ethylene oxide) (PEO) is commonly incorporated into abuse-deterrent medications with further processing to improve mechanical strength. Evaluating the ease by which such tablets can resist crushing is challenging since no compendial or universally-accepted methods exist. Furthermore, the choice of tool used is likely to result in different particle sizes. Therefore, the purpose of this study was to evaluate the ability of different crushing methods (manual and mechanical) and devices to reduce the particle size of a standard PEO-based tablet. Using a Carver press, tablets consisting of 80mg acetaminophen and 320mg high molecular weight PEO (Polyox® WSR coagulant) were made under 2000 pounds of compression. Tablets were then manipulated by manual (pill crusher and pestle-mortar) and mechanical (ball mill and high shear grinder) methods for one minute (n=3). The resultant mass was separated by particle size above and below 500 microns using sieve analysis. It was found that ball mill and pestle-mortar respectively generated 18.1± 0.7and 16.3±2.0 % of particles larger than 500 microns, whereas pill crusher and high shear grinder generated about three times as much such particles, 57.5±1.3 and 54.5±0.6%, respectively. Further analysis of particle size showed tablets crushed using a pill crusher or high shear grinder displayed wide size distributions compared to narrower distributions obtained using a pestle-mortar or ball mill. It was concluded that the type of tool (manual or mechanical) used to perform crush resistance studies is important to show the level of resistance to particle size reduction.

Objective: Epidural steroid injections are one of the effective methods of conservative therapy for low back pain, but the results varied greatly. In order to improve the therapeutic results, we have adopted a highly selective lateral recess injection for the treatment of low back pain. Methods: 150 patients with low back pain (L3, 4, 5, S1) were selected aged from 35 to 80 years with VAS score 9-4 and weight of 50-100 kg. Patients were in prone position on the DSA bed with a thick pillow under the belly pad and the related nerve root was located according to the patient's body surface area. With X-ray anchor and routine sterile drape the mark were determined and the puncture point was injected with lidocaine 1% for topical anesthesia. Under DSA guidance, the ipsilateral medial margin of small joint penetration by breaking the ligament flavum was injected of contrast to confirm the edema area of nerve root of lateral recess. 10 ml of 8% hypertonic saline was injected and five minutes later 20ml of anti-inflammatory and analgesic solution was injected. The treatment was over after the patient status and pain relief were confirmed. Results: Before operation and 20 minutes after operation VAS score was 7.8±1.6 and 3.4±2.0, respectively, in all cases, which indicated the statistics differences (p≤0.05).After 2 weeks, the phone follow-up showed VAS score dropped to 2.4±1.2, which had no statistics differences compared with 20 minutes after operation but statistics differences (p≤0.01) with before operation. After 1 month the follow-up showed VAS score 2.4±2.1, which had statistics differences compared with before operation but no statistics differences compared with those of 20 minutes after operation and 2 weeks after operation. Within 1 week 3 patients had facial flushing, considering the possibility of drug-induced, but disappeared after 1 week without any other postoperative complications and the review of blood was normal. Conclusion: Compared with conventional epidural injection method the lateral recess steroid injection has a better short-and long-term pain relief for the treatment of low back pain.

Matt McCarty, MD is a board certified, fellowship Anesthesiologist with additional subspecialty certification in Pain Medicine practicing in Austin Texas. After a 14 year of successful career in anesthesiology in Tyler Texas, he decided to pursue a pain fellowship at the University of South Florida. Since moving to Austin, he has practiced interventional pain medicine utilizing a multidisciplinary approach involving medication therapy with monitoring, spinal interventions as well as physical and behavioral health therapy. Intrigued by the variable patient response to pain medication and the likely interplay of genetic factors in producing adverse drug events and addiction he founded and developed Genotox Labs. Genotox Labs is a CLIA certified high complexity lab specializing in pharmacogenomic and toxicology confirmation testing.

Urine drug testing (UDT) continues to be the federally recognized gold standard for workplace monitoring and the preferred method in pain management medication monitoring programs. Sample validity testing utilizing temperature, specific gravity, pH and creatinine are used as means of detecting tampering with a UDT. These tests fail to distinguish human urine substitution samples or the use of synthetic urine. This tampering can occur in an unwitnessed sample collection environment. In this setting, we propose a method to match the sample with the individual utilizing donor genetics thereby improving the validity of an unwitnessed sample collection. In this study, we have developed an enhanced validity test, ToxID, to successfully match the urine specimen with its donor. To evaluate the test sensitivity and specificity, a double blind test was performed. A total of 47 individuals donated their buccal cell and urine samples. The samples were collected by two individuals who are not involved in the sample testing and data analysis. They put the urine and buccal cell sample in pairs of matched (positive-matched) and miss matched (negative-matched) and also substituted a few urine samples with synthetic urine. The resulted paired samples were processed and tested. Out of the 47 samples, 3 urine samples failed to produce reliable genotyping results due to poor DNA quality and were omitted from the data analysis. For the remaining 44 paired samples, the assay correctly identified the 10 negative-matched pairs with three of the urine samples being synthetic urine. None of the positive-matched pairs were miss-identified as negative-matched. Therefore the ToxID test has 100% sensitivity and 100% specificity. ToxID is be a valuable validity tool for urine drug testing when sample collection is performed in an unwitnessed environment.

Chukwuma O Agubata completed his PhD in 2014 from University of Nigeria, Nsukka, Nigeria. He is a lecturer in department of Pharmaceutical Technology and Industrial Pharmacy in the university. He is a pharmacist and member of Drug Delivery and Nanomedicines Research group. He has published more than 13 papers in reputed journals and has reviewed manuscripts for different journals.

Piroxicam is a drug used in pain management and its effectiveness depends on dissolution rate and consequently, bioavailability. The objectives of this study are to improve the solubility, dissolution rate and stability of Piroxicam. Goat fat was extracted from the adipose tissues of goat (Capra hircus) by wet rendering while irvingia fat was extracted from Irvingia gabonensis var excelsa (Irvingia wombolu) using petroleum ether (40-60°C). Piroxicam structured lipid carriers (LCs) were formulated using melt homogenization (60°C) of lipid matrices (5 %w/w) comprising goat fat and irvingia fat at 3:1 and 4:1 ratios, Labrasol® solution (1.5 %w/w) and sorbic acid (0.1 %w/w) in distilled water. The lipid carriers were characterized by drug encapsulation efficiency, yield, particle size, thermal properties, drug release and diffusion. The yield and particle size of the LCs were 98% and 4 µm, respectively, while the drug encapsulation efficiency of 4:1 and 3:1 LCs were 95% and 97%, respectively. All the formulations were stable. The drug delivery systems showed controlled release of Piroxicam and 3:1 goat fat/irvingia fat LCs showed higher delivery, releasing 49.8% of the drug after 8h. Structured homolipid carriers can be used for improved delivery of Piroxicam which may increase the effectiveness of the drug in pain management.

Background: Suprascapular nerve block is a common procedure for management of shoulder pain. However, theaccuracy of finding the exact suprascapular notch by ultrasonography remains controversial. Objective: To define the location of the suprascapular notch by surface landmark in patients and to assess the accuracy of suprascapular notch detection by ultrasonography in cadavers. Methods: Patients who underwent ultrasonography and suprascapular nerve block were enrolled in this study. Moving the probe, the suprascapular notch was identified. The length between the medial border of scapula and the posterior angle of acromion and the ratio of the length between the medial border of scapular and the suprascapular notch to the length between the medial border of scapula and the posterior angle of acromion as well as the depth between the surface and the suprascapular notch were measured. In cadavers, dyes were injected around suprascapular notch under ultrasound guidance. Dissection was done to assess the accuracy of suprascapular notch detection by ultrasonography. Results: 36 men and 62 women were included. The length between the medial border of scapula and the posteriorangle of acromion and the ratio of the length in men and women were 13.13 ± 1.08 cm, 0.59 ± 0.04, 12.15±0.90 cm and 0.60±0.04, respectively. The depths of suprascapular notch in men and women were 3.60±0.35 cm and 3.14±0.36 cm respectively. 9 scapulars in five fresh cadavers were included. All of nine injections were shown around suprascapular notch. Conclusions: This study suggests suprascapular notch detection by ultrasonography would be accurate.

A simple, precise, and accurate HPLC method has been developed and validated for assay of combined dosage form of Paracetamol and Thiocolchicoside in commercial pharmaceutical dosage form. Reversed-Phase liquid chromatographic analysis was performed on a BDS hypersil C18, 250mm × 4.6mm, 5μ(particle size), Thermo scientific column using Potassium Dihydrogen phosphate: Methanol (40:60, v/v) as eluent. The flow rate of the mobile phase was adjusted to 1.0 ml/min and the injection volume was 20 μl. Detection performed at 247nm. The retention time of Paracetamol and Thiocolchicoside were found to be 3.27 and 5.50 respectively. The method was validated for linearity, precision, accuracy, robustness. Response was a linear function of drug concentration in the range with 250-750 μg/ml for paracetamol and 1-3μg/ml for thiocolchicoside. Intraday and Interday precision were determined. Accuracy of Paracetamol and thiocolchicoside was found between 99-100%.All analytical validation parameters were determined by following the ICH guidelines and its limit. The developed method proclaimed to be precise and robust for the estimation of Paracetamol and Thiocolchicoside in their combined dosage form. Keywords: RP-HPLC, Paracetamol, Thiocolchicoside, Method Validation.