Advanced formulation design: improving drug therapies for the management of severe and chronic pain.

College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA.
Drug Development and Industrial Pharmacy (Impact Factor: 2.01). 03/2008; 34(2):117-33. DOI: 10.1080/03639040701542200
Source: PubMed

ABSTRACT Chronic pain is a condition affecting a vast patient population and resulting in billions of dollars in associated health care costs annually. Sufferers from severe chronic pain often require [correction of requite] twenty-four hour drug treatment through intrusive means and/or repeated oral dosing. Although the oral route of administration is most preferred, conventional immediate release oral dosage forms lead to inconvenient and suboptimal drug therapies for the treatment of chronic pain. Effective drug therapies for the management of chronic pain therefore require advanced formulation design to optimize the delivery of potent analgesic agents. Ideally, these advanced delivery systems provide efficacious pain therapy with minimal side effects via a simple and convenient dosing regime. In this article, currently commercialized and developing drug products for pain management are reviewed with respect to dosage form design as well as clinical efficacy. The drug delivery systems reviewed herein represent advanced formulation designs that are substantially improving analgesic drug therapies.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The pharmacokinetics of a once-daily formulation of tramadol (Tramadol Contramid OAD 200-mg tablets) following single-dose and multiple-dose administration was compared with that of an immediate-release product (tramadol IR 50-mg tablets) in 2 separate studies. In both studies, AUC parameters met bioequivalence criteria, whereas C(max) of Tramadol Contramid OAD was lower than that of tramadol IR following a 200-mg daily dosage. After single-dose administration, the mean tramadol concentration at 1 hour postdose was within the range associated with analgesic efficacy (>100 ng/mL), and the mean concentration remained above this level for the remainder of the dosing interval. Steady state was attained within 48 hours following multiple-dose administration. Tramadol Contramid OAD provides a rapid rise in plasma concentrations and an equivalent daily systemic exposure as tramadol IR, with a reduction in peak plasma concentrations.
    The Journal of Clinical Pharmacology 05/2010; 50(5):544-53. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Approximately 3.8 million patients annually receive extended-release (ER) or long-acting opioid prescriptions in the outpatient setting, around half of which are written by primary care physicians. Compared with short-acting, immediate-release (IR) formulations, ER and oral long-acting opioid analgesics are associated with clinical advantages, such as extended periods of time during which drug plasma levels are within the therapeutic range, decreased peak-to-trough fluctuations, and prolonged analgesia over the dosing period. Additionally, ER opioids offer a more convenient, less frequent dosing regimen to chronic pain patients who are often taking several concomitant medications. The increased utilization of ER opioids has been accompanied by a rise in the misuse and abuse of these formulations. Certain pharmacokinetic parameters (e.g., longer time to maximum drug plasma concentration, lower maximum drug plasma concentration) may decrease the abuse potential of intact ER opioids by limiting the positive subjective and reinforcing effects relative to IR formulations. Putative abuse-deterrent formulations have also recently been introduced to impede physical manipulation of these formulations, or reduce the harm resulting from such behavior. Such formulations may represent an incremental advance to reduce non-oral forms of abuse. This article reviews the pharmacokinetic profiles and abuse-deterrent features of newer ER opioid analgesics for the treatment of moderate to severe chronic pain.
    Journal of Pain & Palliative Care Pharmacotherapy 03/2013; 27(1):49-61.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic pain is a common healthcare problem worldwide that ranks as a predominant reason for consulting a physician, yet effective management of chronic pain remains suboptimal, often resulting in unnecessary suffering and decreased quality of life, lost productivity and excessive healthcare costs. To overcome the challenges associated with the management of chronic pain, increased awareness and both patient and physician education are required. Improving physician knowledge of pain assessment and management guided by recommendations for a comprehensive, multifactorial, personalised treatment approach involving pharmacological and non-pharmacological approaches is key to achieving effective pain relief. Guidelines for the management of non-cancer and cancer pain recommend thorough patient assessment before individualized therapy based on the type and intensity of pain. The availability of mechanism-specific analgesics has facilitated improvements in the treatment of chronic non-cancer pain, which may be of neuropathic, muscle, inflammatory, mechanical/compressive or mixed origin. Stepwise escalation of analgesic therapy (paracetamol, non-steroidal anti-inflammatory drugs, mild to strong opioids) according to the World Health Organization's three-step pain ladder remains the standard approach for the selection of treatment for chronic cancer pain, although there is now a greater awareness of the requirements for effective administration of opioids including dose titration, use of short versus long-acting opioids, opioid rotation, management of adverse effects, and ongoing monitoring. Selection of an effective, appropriate, personalized analgesic regimen for patients with chronic pain is achievable and is expected to enhance compliance, overall functioning and quality of life.
    Clinical Drug Investigation 02/2012; 32 Suppl 1:21-33. · 1.70 Impact Factor