More user-friendly systems being considered include the device illustrated in Figure 3. It comprises an array of nano-sized needles that perforate the skin barrier but do not come in contact with nerve endings on blood vessels . It is claimed that the delivery system is suitable for anesthetic administration, insulin delivery and vaccination. Suitability for ambulatory patients could greatly expand opportunities for parenteral delivery.
Skin presents a formidable barrier to passage of drugs.
Drugs and the Pharmaceutical Sciences - Routledge
Hence it has historically been restricted to unionized compounds with the right aqueous and oil-solubilities, were low dose and not irritant or sensitizing. Absorption and onset of activity was slow. Nevertheless, a wide range of drugs including estradiol, clonidine, nicotine and testosterone are available in transdermal presentations [18,19].
Rotigatine, a novel drug to treat Parkinsonism and Restless Leg Syndrome was formulated as a transdermal patch by first intent. The latter technique involves delivering thermal pulses to the skin . These cause transient changes to permeability by formation of micro channels. A patch subsequently applied delivers the drug. Insulin levels following such delivery are shown in Figure 4.
Iontophoresis delivers drug under an electrical potential gradient, either by electrorepulsion of ionized drugs or electro-osmosis providing cation selectivity due to negatively charged skin . Rate of delivery can be controlled by varying formulation pH, drug concentration and current density if there is a linear relationship between applied current and drug flux. The analgesic fentanyl hydrochloride for treating post-operative pain provides the patient with capability to increase or decrease dose depending on pain by adjusting the delivery current .
Some peptide drugs can also, reputedly be delivered transdermally in a variety of profiles under the influence of electrical current . Drug is propelled at high speed speed of sound from a piston and into the skin. Claimed advantages concern adaptability. There is also the possibility that drug could be liquefied before delivery.
Programs for future transdermal delivery seek to combine miniaturization, information collection and translation systems with enhanced delivery capability such that diagnostic and delivery reside in the same device.
Such possibilities suggest that transdermal delivery has a bright future as a non-invasive way of delivering appropriate molecular structures, particularly for the elderly where self-medication can be challenging. Some low dose drugs are delivered intranasally, across buccal mucosa or to the lungs via inhalation. Combinations of corticosteroid and long acting beta agonists are widely used in asthma, as orally inhaled powders and are highly effective. The port of entry for such inhaled products presents many challenges due to the labyrinthine nature of oro-laryngeal passages and the variable inspiratory capability of the asthmatic patient.
Many excellent delivery devices have been developed to overcome such challenges and propellant-free powder-based preparations are now available. Future work might concern removing excipients from inhaled powder products to reduce the payload of solids to the lung. The available surface area for absorption is limited and absorption is likely to be variable. The route is likely to be limited to low dose drugs with shallow dose response relationships.
However, some biopharms are likely to meet such requirements. There may be opportunities for novel delivery devices providing more consistent and convenient delivery. Longer age spans in developed societies are making age-related conditions increasingly prominent, with accompanying challenges to drug delivery .
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It presents obvious site-specific delivery challenges and current treatments are not very effective. Intravitreal administration currently seems to be the favored mode of drug administration, acting as a drug reservoir for delivery to the retina [Figure 7 and 25, 26]. The consistency of vitreous humor changes with aging, raising uncertainties concerning drug delivery diffusion to the retinal surface. Treating patients of all age groups with a standard dosing regimen would seem inappropriate in the light of such age differences .
There is a need then for better intra-ocular delivery and possibly better maintenance of drug concentrations at the retina. There is much scope for novel approaches in the area. Treatments and dosing paradigms evolve as knowledge is generated by clinical experience and new molecular biology insights. Antibacterials are a case in point. The accepted paradigm was that antibiotic levels at the site of infection needed to exceed their minimum inhibitory concentration MIC throughout the dosage interval.
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This provides a revised target plasma level for dosage form design, and an opportunity for reformulation . Treating patients with multiple drugs can provide better outcomes in cancer care. However, the sequence and timing of dosing can be important. Recent preclinical studies at Massachusetts Institute of Technology showed better outcomes in breast cancer when the Epidermal Growth Factor Receptor Inhibitor, Erlotinib was administered hours prior to doxorubicin dosing: Cancer cell apoptosis was dramatically increased compared to simultaneous administration.
Clinical studies are planned .
ORAL CONTROLLED RELEASE DRUG DELIVERY SYSTEM- A REVIEW
Institutional cancer care utilizing staggered treatment may not require sophisticated drug delivery systems. However, if similar requirements emerge for chronic, non-terminal ambulatory treatments control of drug delivery needs ideally to be incorporated in the dosage form to improve compliance and convenience.
Advances in understanding of physiological and pathological processes are likely to place greater emphasis on preventative medicine. This, in turn will probably drive the need for medications that are nonintrusive, compliance-friendly and can be delivered in synchrony with other medications that are being taken for the same or separate clinical conditions. Drug delivery needs to be controlled appropriately.
Challenges to do this are not inconsiderable but the rewards for the success will be great. There is now ample evidence that the mode of drug dosage, with respect to rate, time and place of release can influence efficacy. It is highly desirable if not essential therefore that such variables are explored when seeking and developing novel drugs. Fortunately, diagnostic and delivery devices are becoming increasingly available for exploring possibilities for enhancing performance by optimized drug release and targeting. It may become increasingly common for drug to be used in conjunction with one or more diagnostics.
The ideal scenario is that the diagnostic provides continuous monitoring of the condition, with appropriate drug delivery in response. Such systems are being envisioned as future ways of controlling drug release. The cost of such sophisticated devices will be a concern for reimbursing organizations. However, if the net outcome is better treatment, it should result in lower overall cost of healthcare.
As populations in developed countries age, and as preventative medicine assumes greater prominence, the need for customizing and controlling drug release can only increase. Exciting possibilities lie ahead for dosage form design and device engineer specialists and for patients. Surgical Res 95 J Drug Targeting 17 Craft S et al. Neurol 69 1 , 29— Martin R. Sheer F et al.
Moore JG. Rhythms and Therapeutics of Diseases of the Gastrointestinal Tract. The Pharmaceutical Press Svanes R Causes of death in patients with peptic ulcer perforation: a long term followup study; Scand. Gastroenterol 34 F www. Ansel HC, Allen L. V, Popovich NG. Acta Pharm 59; — Patel YR Drug Delivery in Diabetes. Making Effective Treatment Tolerable. Iontophoretic Transport across the Skin. Viscusi ER et al. J Amer Med Assoc 11 Edelhauser FF et al.
Basic Research to Clinical Applications. Invest Ophthalmology and Visual Science 51 11 Biodrugs 20 3 Craig WA. Pharmacokinetic and Pharmacodynamic Factors in Antimicrobial Research. Springer Science and Business Media. Lee MJ et al:. Cell 49 4 Professor Martini has occupied many roles in Industry from Senior Director of Preclinical and Pharmaceutical Development for Emerging Markets and Asia Pacific at GlaxoSmithKline to the development of dosage forms to the design and successful implementation of technological platforms e.
His research interests include the use of ultrasonic processing technology to fabricate medical devices and pharmaceutical dosage forms, the design of dosage form concepts for delivering personalized medicines and the development of biopharmaceuticals. Patrick J.
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He worked in the Pharmaceutical Industry for 43 years, in the UK and US, playing major technical and managerial roles in the commercialization of 16 Novel Drug Products. Publications concern drug and product stability, enhancing drug absorption and repurposing mature pharmaceutical products.
Sarah Ibrahim, Ph. Ibrahim received her Ph. She has 3 years of experience in the Pharmaceutical industry in the USA in the area of formulation and development.
She has published in peer-reviewed journals and is a co-inventor in a number of patent applications. Keep up with our latest articles, news and events. Such optimization may well help reduce the alarming attrition rates that are now prevalent in new drug development. Controlled Release in Oral Drug Delivery provides chapters, dealing with all facets of the above subject matter, and its challenges.
The contents provide a unique blend of cutting edge knowledge, data on materials and practical experiences. It is essential text for students, researchers and industrial engineering, formulation and manufacturing technologists as well as quality testing and control functions. Clive Wilson is the J. Major areas of research have been the study of the behaviour of drug formulations in man.
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