Pharmacy World and Science

, Volume 18, Issue 5, pp 153–162 | Cite as

Advanced and controlled drug delivery systems in clinical disease management

  • J. R. B. J. Brouwers


Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted.

Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative colitis and distally localized Crohn's disease. In cardiology the more classic controlled release systems have improved patient compliance and decreased side effects. In the treatment of intractable pain the spinal and transdermal route is well documented.

In neurology the flattened peak-through levels of antiepileptic drugs and anti Parkinson's drugs represents a more predictable kinetic profile.

Tracheal delivery of corticosteroids and sympaticomimetics in asthma and Chronic Obstructive Pulmonary Disease is fully accepted in clinical practice: delivery by this route results in better efficacy and a better safety profile.

In gynaecology the delivery of pulsatile hormones (LHRH) is used for pregnancy induction, while transdermal oestrogens are promising in the prevention of osteoporosis.

In surgical practice the use of antibiotic impregnated bone cement and antibiotic impregnated biodegradable collagens is well established.

To prevent infections intravascular catheters coated with heparin or antibiotics are used.

In ophthalmology the Ocusert® systems provide a controlled release of different drugs in the eye.

Most spectacular is the clinical introduction of the first liposomal drugs: amfotericine B and daunorubicine. Liposomal formulations of these drugs have enhanced activity and decreased toxicity compared to conventional formulations.


Advanced drug delivery Controlled drug delivery Clinical practice Review 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Montague MJ. Biotechnology CE Series: Biotechnology and the future of medicine. Pharm Pract News 1993 (jan.); p3:p13:p31.Google Scholar
  2. 2.
    DavisSS. Delivery for biopharmaceuticals. J Pharm Pharmacol 1992: 44 (suppl. 1):186–90.Google Scholar
  3. 3.
    MorrowJD. The oral cephalosporins: a review. Am J Med Sci 1992;303:35–9.Google Scholar
  4. 4.
    BeglingerC, DreweJ, KisselT. The absorption site of cyclosporin in human gastro-intestinal tract. Br J Clin Pharmacol 1993; 33: 39–43.Google Scholar
  5. 5.
    TrullAK, TanKK, TanL, AlexanderGJ, JamiesonNV. Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion. Brit J Clin Pharmacol 1995;39:627–31.Google Scholar
  6. 6.
    PardridgeWM. Preface: overview of brain drug delivery. Adv Drug Deliv Rev 1995; 15: 1–3.Google Scholar
  7. 7.
    DelhaasEM, BrouwersJRBJ. Intrathecal baclofen overdose: report of 7 events in 5 patients and review of literature. Int J Clin Pharmacol Ther Tox 1991; 29: 274–80.Google Scholar
  8. 8.
    AlbrightAL, BarronWB, FasickMP, PolinkoP, JanoskyJ. Continuous intratecal baclofen infusion for spasticity of cerebral origin. JAMA 1993; 270: 2475–7.Google Scholar
  9. 9.
    BrouwersJRBJ, CramerK, GulyasJ, Van derKamHJ, SijtsmaJ. Intraportal 5-FU for colorectal hepatic metastasis and adjuvant treatment: a tolerance dose study in: “Progress in Clinical Pharmacy” editors NFMuller & YAHekster. Eur Soc Clin Pharm, Amsterdam Medical Press, Noordwijkerhout 1990; 340–42.Google Scholar
  10. 10.
    Swiss Group for Clinical Cancer Research (SAKK). Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Lancet 1995; 345: 349–53.Google Scholar
  11. 11.
    KoksCHW, BrouwersJRBJ, SleijfferDTh. Regional infusion of fluoropyrimidines for hepatic metastasis of colorectal cancer. Pharm Weekbl [Sci] 1988; 10: 69–75.Google Scholar
  12. 12.
    KemenyN, SeiterK, ContiJA, CohenA, BertinoJR, SigurdsonER, et al. Hepatic arterial floxuridine and leucovorin for unresectable liver metastasis for colorectal carcinoma. Cancer 1994; 73; 1134–42.Google Scholar
  13. 13.
    Braat DDM. Multiple pregnancies in pulsatile GnRH treatment. Thesis Free University of Amsterdam, Amsterdam 1992.Google Scholar
  14. 14.
    RubinsteinA. Microbially controlled drug delivery to the colon. Biopharm Drug Disp 1990; 11: 465–75.Google Scholar
  15. 15.
    BjarnasonI, McPhersonAJ. Delivery, safety and efficacy of 5-aminosalicylate preparations. Inflammopharmacol 1993; 3: 277–87.Google Scholar
  16. 16.
    JarnerotG. New salicylates as maintenance treatment in ulcerative colitis. Gut 1994; 35: 1155–8.Google Scholar
  17. 17.
    ChristensenLA, FallingborgJ, JacobsenBA, AbildgaardK, RasmussenHH, HansenSH, et al. Comparative bioavailability of 5-aminosalicylic acid from a controlled-release preparation and azo-bound preparation. Alim Pharmacol Ther 1994; 8: 289–94.Google Scholar
  18. 18.
    MethaRP. Nephropathy from 5-aminosalicylate preparations. Inflammopharmacol 1993; 2: 297–300.Google Scholar
  19. 19.
    ThuluvathPJ, NincovicM, CalamJ, AndersonM. Mesalazine induced interstitial nephritis. Gut 1994; 35: 1493–6.Google Scholar
  20. 20.
    LöfbergR. New steroids for inflammatory bowel disease. Inflam Bowel Dis 1995; 1: 135–41.Google Scholar
  21. 21.
    MulderCJJ, TytgatGNJ. Review article: topical corticosteroids in inilammatory bowel disease. Alim Pharmacol Therap 1993; 7: 125–30.Google Scholar
  22. 22.
    MellerDDM, MolemaG. Targeting of drug to the liver. Sem Liver Dis 1995; 15:202–56.Google Scholar
  23. 23.
    HillemanDE, BanakarUV. Issue in contemporary drug delivery, Part VI: Advanced cardiac drug formulations. J Pharm Techn 1992; 8: 203–11.Google Scholar
  24. 24.
    WhiteWB, AndersRJ, McIntyreJM, BlackHR, SicaDA and the Verapamil Study Group. Nocturnal dosing of a novel delivery system of verapamil for systemic hypertension. Am J Cardiol 1995; 76: 375–80.Google Scholar
  25. 25.
    BadlerM, HadadS, GolombG, BarelS, SamaraE, SalachOA, et al. Pharmacokinetic analysis of two new sustained release products of dilthiazem designed for twice and once daily treatment. Biopharm Drug Disp 1994; 15: 45–52.Google Scholar
  26. 26.
    MeredithPA, ElliottHL. FDA guidelines on through:peak ratios in the evaluation of antihypertensive agents. United States Food and Drug Administration. J Cardiovasc Pharmacol 1994; 23 (Suppl 5) S26–30.Google Scholar
  27. 27.
    BrouwersJRBJ. Orale toedienings vormen met gereguleerde afgiften. Stichting Anselmus, Heesch, The Netherlands 1989; 49–58.Google Scholar
  28. 28.
    HagenN, FlynneP, HagsH, Mac DonaldN. Guidelines for managing chronic non-malignant pain: opioid and other agents. Can Family Physician 1995; 41: 49–53.Google Scholar
  29. 29.
    DelhaasEM, BrouwersJRBJ. The spinal and epidural administration of narcotic analgesics in cancer patients. Royal Soc Med 1989 Congres Series nr 149: 91–3.Google Scholar
  30. 30.
    LeCorreP, PolardE, ChevannetF, LeVergeR. Morphine-controlled release from microspheres for site-specific delivery (abstract 456). Brit J Anesth 1995; 74 (Suppl 1): 139.Google Scholar
  31. 31.
    OralU, IsikG, OzbekH, GülerI. Intranasal fentanyl administration for postoperative pain (Abstract 458). Intranasal alfentaryl administration for postoperative pain (A459). Brit J Anaesth 1995; 75 (Suppl 1): 139.Google Scholar
  32. 32.
    WongPK, AsburgAJ, WardKM, DonellD, WrayH, StamponeP et al. Fentanyl by metered dose breath-actuated inhaler as analgesic after total abdominal hysterectomy. A clinical evaluation (Abstract 460). Brit J Anes 1995; 74: 140.Google Scholar
  33. 33.
    MaloneyCM, KesnerRK, KlemG, BockenstetteJ. The rectal administration of MS-Contin: clinical implications for use in end-stage cancer. Am J Hospice Palliative Care 1989; 6: 34–5.Google Scholar
  34. 34.
    MoolenaarF, FietsG, VisserJ, MejjerDKF. Prelimary study on the absorption profile after rectal and oral administration of methadone in human volunteers. Pharm Weekbl [Sci] 1984; 6: 237–40.Google Scholar
  35. 35.
    HammingCD, VickersAP, SmithG, GrahamNB, McNeilME. The morphine hydrogel suppository: a new sustained-release rectal preparation. Brit J Anesth 1988; 61: 221–7.Google Scholar
  36. 36.
    ConnoF, RipamontiC, SaitiL, MacEachernT, HansonJ, BrueraE. Role of rectal route in treating cancer pain: a randomized cross-over clinical trail of oral versus rectal morphine administration in opioid-naive cancer patients with pain. J Clin Oncol 1995; 13: 1004–8.Google Scholar
  37. 37.
    SchulzmanSA. Oral transmucosal fentanyl citrate for premedication of children undergoining laceration repair. Ann Emerg Med 1984; 24:1059–64.Google Scholar
  38. 38.
    GerwelsJW. Oral transmucosal fentanyl citrate premedication in patients undergoining outpatient dermatologic procedures. J Dermatol Surg Oncol 1994; 201:823–26.Google Scholar
  39. 39.
    DuncanL, WildsmithJAW. Liposomal local anaesthetics (Editorial). Brit J Anaesth 1995; 75: 260–1.Google Scholar
  40. 40.
    VavraI, PaulusHE. Controlled-release and enteric-coated formulations of NSAIDs. In. therapeutic applications of NSAIDs: subpopulations and new formulations. Editor: J.P.Famaey & H.E.Paulus. Marcel Dekker Inc. New York 1992; p. 373–83.Google Scholar
  41. 41.
    HollanderD. Gastro-intestinal complications of NSAIDs: prophylactic and therapeutic strategies. Am J Med 1994; 96: 274–81.Google Scholar
  42. 42.
    JanknegtR, BrouwersJRBJ, VanRielPLCM. Drug evaluation for non steroidal anti-inflammatory drugs by the SOJA method (Dutch). Ziekenhuisfarmacie (Neth.) 1995; 11: 94–106.Google Scholar
  43. 43.
    Anonymous. Drugs for Parkinson's disease reviewed. Drug Ther Bull 1995; 33: 49–52.Google Scholar
  44. 44.
    DavisJM, MetalonL, WanatabeMD, BlakeL. Depot antipsychotic drugs place in therapy. Drugs 1994; 47:741–773.Google Scholar
  45. 45.
    WHO. Mechanism of action, safety and efficacy of intrauterine devices. WHO Tech Rep Ser no. 753, 1987.Google Scholar
  46. 46.
    NaessenT, PerssonI, ThorL, MallminH, LjunghallS, Berstrom. Maintained bone density at advanced ages after longterm treatment with low dose oestradiol implants. Brit J Obstet Gynaecol 1993; 100:454–9.Google Scholar
  47. 47.
    SandersonPJ. Leading Article: Preventing infections orthopaedic implants. J Antimicrob Chemoth 1989; 24: 277–80.Google Scholar
  48. 48.
    DiMaioFr, HalloranJJ, QualeJM. In vitro elution of ciprofloxacin from polymethylmethacrylate beads. Orth Res 1994; 12: 79–82.Google Scholar
  49. 49.
    BrienPW, SalvataEA, KleinR, BrauseB, SternS. Antibiotic impregnated bone cement in total hip arthroplasty. An in vivo comparison of the elution properties of tobramycin and vancomycin. Clin Orthop 1993; 296: 242–8.Google Scholar
  50. 50.
    GerhartTN, RouxPD, HanffPA, HorowitzGL, RenshawAA, HayesWC. Antibiotic loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomylitis. Orthop Res 1993; 11: 250–5.Google Scholar
  51. 51.
    JörgensenLG. Clinical and pharmacokinetic evaluation of gentamicin containing collagen in groin wound infections. Eur J Vasc Surg 1991; 5: 87–91.Google Scholar
  52. 52.
    HasselbachvonC. Klinik und Pharmakokinetiek von Kollagen-Gentamicin als adjuvante Lokal therapie knöcherner Infektion. Unfallchirung 1989; 93: 459–70.Google Scholar
  53. 53.
    BandijkDF, EssesGE. Prosthetic graft infection. Surg Clin Nort Am 1994; 74: 571–90.Google Scholar
  54. 54.
    BergaminiTM, McCurryTM, BernardJD, HoegKL, CorpusRA, PeytonJC, et al. Antibiotic efficacy against staphylococcus epidermidis adherent to vascular grafts. Vasc Forum 1994; 2: 92–3.Google Scholar
  55. 55.
    Goëau-BrissonnièreO, MercierF, NicolasMH, BacourtF, CoggiaM, LebrautC, et al. Treatment of vascular graft infection by in situ replacement with a rifampicin-bonded gelatin-sealed Dacron graft. J Vasc Surg 1994; 19: 739–44.Google Scholar
  56. 56.
    GoldmannDA, PieGB. Pathogenesis of infections related to intravascular catheterisation. Clin Microbiol Rev 1993; 6: 176–92.Google Scholar
  57. 57.
    AppelgrenP, RansjöU, BindslevL, LarmO. Does surface heparinisation reduce bacterial colonisation of central venous catheters? Lancet 1995; 345: 130 (letter).Google Scholar
  58. 58.
    TebbsSE, ElliotTSJ. Modification onf central venous catheter polymers to prevent in vitro microbial colonisation. Eur J Clin Microbiol Infect Dis 1994; 13: 111–7.Google Scholar
  59. 59.
    RaadI, DarouicheR, HachenR, SacilowskiM, BodeyGP. Antibiotics and prevention of microbial colonisation of catheters. Antimicrob Agents Chemother 1995; 39: 2397–2400.Google Scholar
  60. 60.
    SaettoneMF, SalminenL. Ocular inserts for topical delivery. Adv Drug Deliv Rev 1995; 16: 95–106.Google Scholar
  61. 61.
    ZimmerA, KreuterJ. Microspheres and nanoparticles used in ocular delivery systems. Advanced Drug Deliv Rev 1995; 16: 61–73.Google Scholar
  62. 62.
    MeisnerD, MezeiM. Liposome ocular delivery systems. Advanced Drug Deliv Rev 1995; 16: 75–93.Google Scholar
  63. 63.
    ErnestJT. Intraocular device for cytomegalovirus infection. Lancet 1995; 346: 983–4.Google Scholar
  64. 64.
    BergersJJ, tenHagenTLM, vanEttenEWM, Bakker-WoudenbergIAJM. Liposomes as delivery systems in the prevention and treatment of infectious diseases. PWS 1995; 17: 1–11.Google Scholar
  65. 65.
    DeMarieS, JanknegtR, Bakker-WoudenbergIAJM. Clinical use of liposomal and lipid-complexed amphotericin B. J Antimicrob Chemother 1994; 33: 907–16.Google Scholar
  66. 66.
    TollenaarJ, RingdenO. Lipid formulation of amphotericin B less toxicity but at what economic cost? Drug Safety 1995; 13: 207–18.Google Scholar
  67. 67.
    GraysonLS, HansbroughJF, Zapata-SirventR, RoehrbornAJ, KimT, KimS. Soft tissue infection prophylaxis with gentamicin encapsulated in multi-vascular liposomes: results from a prospective, randomized trial. Crit Care Med 1995; 23: 84–91.Google Scholar
  68. 68.
    OmarRF, DussereN, DésormeauxA, PoulesL, TremblayM, BeauchampD, et al. Liposomal encapsulation of foscarnet protects against hypocalcemia induced by free foscarnet. Antimicrob Agents Chemother 1995; 39: 1973–8.Google Scholar
  69. 69.
    KimS. Liposomes as carriers of cancer chemotherapy: current status and future prospects. Drugs 1993; 46: 618–38.Google Scholar
  70. 70.
    GillPS, EspinaBM, MuggiaF, CabrialisS, TulpuleA, EsplinJA et al. Phase I/II clinical and phartmacokinetic evaluation of liposomal daunorubicin. J. Clin Oncol 1995; 13:996–1003.Google Scholar
  71. 71.
    PresantCA, ScolaroM, KennedyP, BlayneyDW, FlanagenB, LisakJ, et al. Liposomal daunorubicin treatment of HIV associated Kaposi's sarcoma. Lancet 1993; 341: 1242–43.Google Scholar
  72. 72.
    BremH, PlantadosiS, BurgerPC, WalkerM, SelkerR, VickNA, et al. Placebo-controlled trial of safety and efficacy of intra operative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 1995; 345: 1008–12.Google Scholar
  73. 73.
    SiegallCB. Targeted toxins as anticancer agents. Cancer 1994; 74: 1006–12.Google Scholar
  74. 74.
    KennedyFP. Recent developments in insulin delivery techniques: current status and future potential. Drugs 1991; 42: 213–27.Google Scholar
  75. 75.
    PetersAM. The utility of99mTc-HMPAO-leukocytes for imaging infection. Sem Nucl Med 1994; 24: 110–27.Google Scholar
  76. 76.
    DatzFL. Indium-111-labeled leukocytes for the detection of infection: current status. Sem Nucl Med 1994; 24: 92–109.Google Scholar
  77. 77.
    RubinRH, FischmanA. The use of radiolabeled nonspecific immunoglobulin in the detection of focal inflammation. Sem Nucl Med 1994; 24: 169–79.Google Scholar
  78. 78.
    FischmanAJ, BabichJW, RubinRH. Infection imaging with technetium-99m-labeled chemotactic peptide analogs. Sem Nucl Med 1994; 24: 154–168.Google Scholar
  79. 79.
    SahaGB, MclntyreWJ, GoRT. Radiopharmaceuticals for brain imaging. Sem Nucl Med 1994; 24: 324–49.Google Scholar
  80. 80.
    HawkinsRE, LewelynMB, RusselSJ. Adapting antibodies for clinical use. Brit Med J 1993; 305: 1348–52.Google Scholar
  81. 81.
    BuckleyNA, DawsonAH, ReithDA. Controlled-release of drugs in overdose. Drug Saf 1994; 12: 73–84.Google Scholar
  82. 82.
    Anonymous. Controlled release formulations delay and prolong linical effects following overdose. Drugs Ther Persp 1995; 5 (7): 11–13.Google Scholar
  83. 83.
    DavisSS. Delivery systems for biopharmaceuticals. J Pharm Pharmacol 1992; 44 (Suppl 1): 186–90.Google Scholar
  84. 84.
    ChalfinDB, HolbeinMEB, FeinAM, CarlonGC. Cost-effectiveness of monoclonal antibodies to Gram-negative endotoxin in the treatment of Gram-negative sepsis in ICU patients. JAMA 1993; 269: 249–54.Google Scholar
  85. 85.
    WherryJC, PenningtonJE, WenzelRP. Tumor necrosis factor and the therapeutic potential of anti-tumor necrosis factor antibodies. Crit Care Med 1993; 241: S 436–440.Google Scholar
  86. 86.
    HurleyJC. Reappraisal of the role of endotoxin in the sepsis syndrome. Lancet 1993; 341: 1133–5.Google Scholar
  87. 87.
    DeitchEA. Cytokines yes, cytokines no, cytokinesmay be. Crit Care Med 1993; 21: 817–19.Google Scholar
  88. 88.
    BlauHM, SpringerML. Gene therapy a novel form of drug delivery. New Engl J Med 1995; 333: 1204–7.Google Scholar
  89. 89.
    GlennieJL, WoloschukDMM, HallKW. High technology drugs for cancer: the decision process for adding to a formulary. Pharmaco Economics 1993; 4: 405–13.Google Scholar
  90. 90.
    RhoderJ, ThomasG. Nicotine treatment in ulcerative colitis: current status. Drugs 1995; 49: 157–60.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • J. R. B. J. Brouwers
    • 1
  1. 1.Groningen-Utrecht Institute for Drug Exploration (GUIDE), Division of Pharmacokinetics and Clinical Pharmacy, Department of Social Pharmacy and PharmacoepidemiologyState University GroningenGroningenThe Netherlands

Personalised recommendations