Franco, Margarida Cabrita

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DRUG DELIVERY SYSTEMS – A Brief Approachby MARGARIDA CABRITA FRANCOIPL – Instituto Politécnico de LeiriaCDRSP - Centro Para o Desenvolvimento Rápido eSustentado do Produto1 Drug delivery systemsAlthough drug delivery may not attract the attention andpress coverage of some of the other disciplines involved indrug discovery, it is an equally important issue in the de-velopment of a successful product. Besides the choice ofthe active drug substance (active pharmaceutical ingre-dient - API), a responsible decision regarding the routeof administration and dosage form needs to be made. Awrong choice can cause failure of therapy. Dosage formsmay be classified into:• Conventional release;• Modified release which can be delayed, controlledor sustained.The conventional release dosage forms are designed torelease the drug promptly after administration of a bo-lus for immediate release. In contrast, modified releasedosage forms are designed to modulate drug release, de-laying or prolonging the dissolution. Various technologiesmay be employed to promote the gradual release of adrug from a pharmaceutical form.In the conventional therapy, aliquot quantities of adrug are introduced into the system at specified time in-tervals resulting in a considerable fluctuation on drugconcentration levels. However, an ideal dosage regimenwould be the one in which the concentration of the drugis maintained between the limits of the therapeutic win-dow at a constant level throughout all the treatment pe-riod. Both situations can be graphically represented inFigure 1.The basic goal of this kind of therapy is to achieve asteady state blood level that is therapeutically effectiveand non-toxic for an extended period of time. The designof a proper dosage regimen is an important element whenwe want to accomplish this objective. An excellent drugdelivery system provides the right amount of drug or itsactive metabolite to the target, at a time and rate thatoptimizes its effect, without compromising patient safety.Fig. 1 - Immediate versus controlled release dosage forms.(MEC-Minimum effective concentration; MTC-Minimum toxic concentration)in Steve I. Shen, Bhaskara R. Jasti, and Xiaoling Li, Standard Handbook of Biomedical Engineering and Design, MyerKutz (ed), Chapter 22: Design of Controlled-Release Drug Delivery Systems, Copyright The McGraw-Hill Companies,Inc. 2003Scripta-Ingenia, Summer Solstice, June 21, 2014. (ISSN: 2183-6000)m http://cdrsp.ipleiria.pt T (351) 244-569441 B scripta.ingenia@ipleiria.pt Page 121 DRUG DELIVERY SYSTEMSControlling release to meet these requirements can in-volve preventing release or delivery in enzymatically orother hostile environments, targeting a specific locationto enhance therapeutic index, or prolonging delivery tosustain an effect. Delivery on demand may also be re-quired with biosensors linked to a delivery device like adrug reservoir, for example. Pros and cons of controlledDrug Delivery Systems (DDS) can be listed as follows:• Improved patient convenience and compliance dueto less frequent drug administration.• Reduction in fluctuation achieving a steady-statelevel and therefore better control of disease condi-tion.• Increased safety margin of the drug due to bettercontrol of plasma levels.• Maximum utilization of drug enabling reduction intotal amount of dose administered.• Reduction in health care cost through improvedtherapy and shorter treatment period.• Less frequency of dosing and reduction in personneltime to dispense, administer and monitor patients.• Better control of drug absorption can be obtained,since the high blood level peaks that may be ob-served after administration of a single dose corre-sponding to a high bioavailability drug can be re-duced.• Decreased systemic availability in comparison toimmediate release conventional dosage forms; thismay be due to incomplete release or insufficient res-idence time for complete release, for example.• Poor in-vivo/in-vitro correlation.• Possibility of dose dumping due to food interactionwith formulation and thus increased risk of toxicity.• Retrieval of drug is difficult in case of toxicity, poi-soning or hypersensitivity reaction.• The physician has less flexibility in adjusting dosageregimens. This is fixed by the dosage form design.• Economic factors must also be assessed, since morecostly processes and equipment are involved inmanufacturing many of the sustained release forms.Medication delivery to the systemic circulationthrough the skin is an alternative to oral and parenteralroutes of administration. The first Transdermal Drug De-livery Systems (TDDS) or drug loaded patches enteredthe U.S. market in 1979 with the approval of the scopo-lamine patch by the Food and Drug Administration (FDA)for treatment of motion sickness. Today there are morethan twenty different types of medication patches avail-able, and researchers are constantly striving to developadditional and improved methods for transdermal deliv-ery of medications. The great advantage lays on the factthat it avoids first pass metabolism reactions which oc-cur in the liver and gut wall resulting in a decrease ondrug bioavailability. TDDS (transdermal patches or trans-dermal drug delivery systems) are designed to show aperfect adhesion onto healthy and clean skin in order toassure controlled drug delivery into the systemic circu-lation. Problems linked with factors that affect percuta-neous absorption must be studied and solved. This is thepurpose of several research teams working in universitiesall over the world. Actually those problems are connectedwith the following questions:• Drug physicochemical properties: solubility, molec-ular weight, partition coefficient;• Stratum corneum characteristics like thickness andlipophilicity;• Concentration of the drug;• Area of the applied field;• Drug affinity for the skin.Some promoters of percutaneous absorption have beensuggested. Chemical permeation enhancers, iontophore-sis, sonophoresis and even micro or nano needles aregood examples. Different types of delivery systems in-volve different technologies to sustain release and can belisted as shown below:Scripta-Ingenia, Summer Solstice, June 21, 2014. (ISSN: 2183-6000)m http://cdrsp.ipleiria.pt T (351) 244-569441 B scripta.ingenia@ipleiria.pt Page 132 CONTROLLED DRUG DELIVERY AT CDRSP• Matrix systems: the matrix can be hydrophilic orhydrophobic and drug release processes can involveswelling of the polymer in use, drug diffusion andmatrix erosion;• Reservoir systems;• Osmotic pumps;• Other systems – micro or nano sized needle arrays.The improvement and innovation in the developmentof controlled release systems strongly depend on select-ing an appropriate agent capable of controlling drug re-lease. The ideal agents for these preparations should en-sure that the drug is released at the right place in theright dose and at (or during) the required time. In addi-tion, it must be said that with the advances in the fieldof chronobiology, modern drug delivery approaches havebeen elevated to a new concept of chronopharmacology,which is the ability to deliver the therapeutic agent to apatient in a pulsatile profile. New technology for medica-tions delivering in a time-modulated fashion, by bedsideor ambulatory pumps, is being developed to manage hu-man diseases, mainly chronic diseases.Fig 2 - Time cycle when the diseases show their maximum effectin Bisht R., Chronomodulated drug delivery system: A comprehensive review on the recent advances in a new sub-discipline of ’chronopharmaceutics’. Asian J Pharm; 2011; 5:1-82 Controlled Drug Delivery atCDRSPIn our research center, we are trying to “build” a model inwhich levodopa (3,4-Dihydroxy-L-phenylalanine) is en-trapped inside a sodium alginate membrane for skin ad-ministration with a controlled mechanism of delivery. Itis expected that transdermal route would provide a sup-ply of the drug to the blood stream without fluctuationson therapeutic levels. This fact is very important in orderto avoid the typical on-off effects related to the thera-peutics of Parkinson Disease, the disorder in which lev-odopa is still the gold standard. In our labs, we produceand characterize our drug loaded membranes; then, wecarry out the necessary dissolution assays required by thePharmacopoeias and recommended by the drug nationaland international authorities. Finally, specific mathemat-ical models are applied in order to understand the drugrelease mechanism from the polymeric matrix.References[1] Ale I, Lachapelle JM, Maibach HI. Skin tolerability associated with transdermal drug delivery systems: anoverview. Adv Ther. 2009; 26:920–35Scripta-Ingenia, Summer Solstice, June 21, 2014. (ISSN: 2183-6000)m http://cdrsp.ipleiria.pt T (351) 244-569441 B scripta.ingenia@ipleiria.pt Page 142 CONTROLLED DRUG DELIVERY AT CDRSP[2] Bisht R. Chronomodulated drug delivery system: A comprehensive review on the recent advances in a new sub-discipline of ’chronopharmaceutics’. Asian J Pharm 2011; 5:1-8[3] Hong I, Gabay M, Ladolce A. Safety concerns involving transdermal patches and magnetic resonance imaging(MRI). Hosp Pharm. 2010; 45:771–8[4] Goole J., Amighi K., “Levodopa delivery systems for the treatment of Parkinson’s disease: an overview”, Interna-tional Journal of Pharmaceutics. 2009; 380:1-15[5] Luigi G. Martini, Patrick J. Crowley, Sarah Ibrahim, Controlling Release from Dosage Forms: The Future, Ameri-can Pharmaceutical Review, 2012, June 25[6] Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv. 2004; 4:308–12[7] Steve I. Shen, Bhaskara R. Jasti, and Xiaoling Li, Standard Handbook of Biomedical Engineering and Design,Myer Kutz (ed), Chapter 22: Design of Controlled-Release Drug Delivery Systems, Copyright The McGraw-Hill Com-panies, Inc. 2003[8] Tanner T., Marks R. Delivering drugs by the transdermal route: review and comment. Skin Res Technol. 2008;14:249–60PONTIAC DEBUTS 2007 SOLSTICE GXP AT LA AUTO SHOWThe GXP version of the Solstice debuted at the Los Angeles Auto Show in January 2006.The Pontiac Solstice Coupes are considered to be quite rare: There were a total of 1,266 Solstice Coupesthat were able to be manufactured before the production line in Wilmington, Delaware was shut down:102 pre-production 2009 models, 1,152 sequentially-vin’d regular production 2009 models, and 12 pre-production 2010 models. This is in contrast to over 64,000 of the Pontiac Solstice Convertibles that weremanufactured.— WikipediaScripta-Ingenia, Summer Solstice, June 21, 2014. (ISSN: 2183-6000)m http://cdrsp.ipleiria.pt T (351) 244-569441 B scripta.ingenia@ipleiria.pt Page 15

Drug delivery systems : a brief approach

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Drug delivery systems : a brief approach

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