An in-depth overview of controlled drug delivery systems: Present developments and prospective advancements

Ibrahim Abdullah Hamzy; Abdulelah Ibrahim Alqhoson; Anas Mohammed Aljarbou; Mohammed Abdulrahman Alhajri

doi:10.53730/ijhs.v6nS10.15096

Authors

Ibrahim Abdullah Hamzy KSA, National Guard Health Affairs
Abdulelah Ibrahim Alqhoson KSA, National Guard Health Affairs
Anas Mohammed Aljarbou KSA, National Guard Health Affairs
Mohammed Abdulrahman Alhajri KSA, National Guard Health Affairs

Keywords:

Controlled drug delivery systems, pharmaceutical technology, drug release kinetics, biomaterials, nanocarriers, stimuli-responsive polymers

Abstract

Background: Drug delivery systems (DDS) are crucial in modern medicine for optimizing the therapeutic efficacy and safety of pharmaceutical agents. Traditionally, direct use of active pharmaceutical ingredients (APIs) poses challenges such as dosing accuracy, stability, and patient compliance. Controlled drug delivery systems have emerged to address these issues by releasing drugs at a controlled rate, thereby enhancing therapeutic outcomes and minimizing side effects. Aim: This article aims to provide a comprehensive overview of current advancements and future prospects in controlled drug delivery systems. It explores various DDS technologies, their mechanisms, and their impact on drug efficacy and patient adherence. Methods: The review synthesizes data from recent research on drug delivery systems, focusing on their classification, design considerations, and performance. It discusses the pharmacokinetics of drug release, including absorption, distribution, metabolism, and excretion, and evaluates different controlled release mechanisms such as dissolution-controlled, diffusion-controlled, and osmotic pressure-controlled systems. Results: Controlled DDS have evolved significantly from the first-generation systems that relied on basic mechanisms like dissolution and diffusion to advanced technologies involving stimuli-responsive biomaterials. These systems now include innovations such as nanoparticle-based delivery, self-regulating devices, and long-term non-invasive methods for proteins and nucleic acids.

Downloads

Download data is not yet available.

References

Langer, R. Drug delivery and targeting. Nature 1998, 392, 5–10. DOI: https://doi.org/10.1038/32020

Benoit, D.S.; Overby, C.T.; Sims, K.R., Jr.; Ackun-Farmmer, M.A. Drug delivery systems. In Biomaterials Science; Elsevier: Amsterdam, The Netherlands, 2020; pp. 1237–1266. DOI: https://doi.org/10.1016/B978-0-12-816137-1.00078-7

Langer, R. New methods of drug delivery. Science 1990, 249, 1527–1533. DOI: https://doi.org/10.1126/science.2218494

Chaudhari, S.P.; Patil, P.S. Pharmaceutical excipients: A review. IJAPBC 2012, 1, 21–34.

Jain, K.K. An overview of drug delivery systems. Drug Deliv. Syst. 2020, 2059, 1–54 DOI: https://doi.org/10.1007/978-1-4939-9798-5_1

Patel, H.; Shah, V.; Upadhyay, U. New pharmaceutical excipients in solid dosage forms-A review. Int. J. Pharm. Life Sci. 2011, 2, 1006–1019.

Kalasz, H.; Antal, I. Drug excipients. Curr. Med. Chem. 2006, 13, 2535–2563. DOI: https://doi.org/10.2174/092986706778201648

Ku, M.S. Use of the biopharmaceutical classification system in early drug development. AAPS J. 2008, 10, 208–212. DOI: https://doi.org/10.1208/s12248-008-9020-0

Verma, P.; Thakur, A.; Deshmukh, K.; Jha, A.; Verma, S. Research. Routes of drug administration. Int. J. Pharm. Stud. Res. 2010, 1, 54–59.

Augsburger, L.L.; Hoag, S.W. Pharmaceutical Dosage Forms-Tablets; CRC Press: Boca Raton, FL, USA, 2016. DOI: https://doi.org/10.1201/b15115

Qiu, Y.; Chen, Y.; Zhang, G.G.; Yu, L.; Mantri, R.V. Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice; Academic Press: Cambridge, MA, USA, 2016.

Mahato, R.I.; Narang, A.S. Pharmaceutical Dosage Forms and Drug Delivery: Revised and Expanded; CRC Press: Boca Raton, FL, USA, 2017.

Bora, A.; Deshmukh, S.; Swain, K. Recent advances in semisolid dosage form. Int. J. Pharm. Sci. Res. 2014, 5, 3596.

Niazi, S.K. Handbook of Pharmaceutical Manufacturing Formulations: Volume Four, Semisolid Products; CRC Press: Boca Raton, FL, USA, 2019 DOI: https://doi.org/10.1201/9781315102856

Mahalingam, R.; Li, X.; Jasti, B.R. Semisolid dosages: Ointments, creams, and gels. Pharm. Manuf. Handb. 2008, 1, 267–312.

Allen, L.V., Jr. Basics of compounding: Tips and hints, Part 3: Compounding with ointments, creams, pastes, gels, and gel-creams. Int. J. Pharm. Compd. 2014, 18, 228–230.

Prausnitz, M.R.; Langer, R. Transdermal drug delivery. Nat. Biotechnol. 2008, 26, 1261–1268. DOI: https://doi.org/10.1038/nbt.1504

Prausnitz, M.R.; Mitragotri, S.; Langer, R. Current status and future potential of transdermal drug delivery. Nat. Rev. Drug Discov. 2004, 3, 115–124. DOI: https://doi.org/10.1038/nrd1304

Al Hanbali, O.A.; Khan, H.M.S.; Sarfraz, M.; Arafat, M.; Ijaz, S.; Hameed, A. Transdermal patches: Design and current approaches to painless drug delivery. Acta Pharm. 2019, 69, 197–215. DOI: https://doi.org/10.2478/acph-2019-0016

Dhiman, S.; Singh, T.G.; Rehni, A.K. Transdermal patches: A recent approach to new drug delivery system. Int. J. Pharm. Pharm. Sci. 2011, 3, 26–34.

Perrigo. Transderm-Scop, Scopalamine Transdermal Patch. Available online: https://investor.perrigo.com/2019-10-03-Perrigo-Announces-the-Relaunch-of-the-AB-Rated-Generic-Version-of-Transderm-Scop-R-1-5-MG (accessed on 2021).

Gad, S.C. Semisolid dosages: Ointments, creams and gels. In Pharmaceutical Manufacturing Handbook: Production and Processes; John Wiley & Sons: Hoboken, NJ, USA, 2008; Volume 5, pp. 267–312. DOI: https://doi.org/10.1002/9780470259818.ch9

Rubio-Bonilla, M.V.; Londono, R.; Rubio, A. Liquid dosage forms. In Pharmaceutical Manufacturing Handbook: Production and Processes; John Wiley & Sons: Hoboken, NJ, USA, 2008; Volume 5, pp. 313–344. DOI: https://doi.org/10.1002/9780470259818.ch10

Kumar, R.S.; Yagnesh, T.N.S. Pharmaceutical suspensions: Patient compliance oral dosage forms. World J. Pharm. Pharm. Sci. 2016, 5, 1471–1537.

Kalantzi, L.; Reppas, C.; Dressman, J.; Amidon, G.; Junginger, H.; Midha, K.; Shah, V.; Stavchansky, S.; Barends, D.M. Biowaiver monographs for immediate release solid oral dosage forms: Acetaminophen (paracetamol). J. Pharm. Sci. 2006, 95, 4–14. DOI: https://doi.org/10.1002/jps.20477

Sears, W. Linctuses. Practitioner 1951, 166, 91–92. DOI: https://doi.org/10.2307/935036

Payne, K.; Roelofse, J.; Shipton, E. Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years—A pilot study. Anesth. Prog. 2002, 49, 109.

Van Schoor, J. Using gargles and mouthwashes: Medicine cupboard. SA Pharm. Assist. 2011, 11, 26.

Shargel, L.; Andrew, B.; Wu-Pong, S. Applied Biopharmaceutics & Pharmacokinetics; Appleton & Lange Stamford: Stamford, UK, 1999; Volume 264.

Jambhekar, S.S.; Breen, P.J. Basic Pharmacokinetics; Pharmaceutical Press: London, UK, 2009; Volume 76.

Fleisher, D.; Li, C.; Zhou, Y.; Pao, L.-H.; Karim, A. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clin. Pharmacokinet. 1999, 36, 233–254. DOI: https://doi.org/10.2165/00003088-199936030-00004

Obata, K.; Sugano, K.; Saitoh, R.; Higashida, A.; Nabuchi, Y.; Machida, M.; Aso, Y. Prediction of oral drug absorption in humans by theoretical passive absorption model. Int. J. Pharm. 2005, 293, 183–192. DOI: https://doi.org/10.1016/j.ijpharm.2005.01.005

Hubatsch, I.; Ragnarsson, E.G.; Artursson, P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat. Protoc. 2007, 2, 2111–2119. DOI: https://doi.org/10.1038/nprot.2007.303

Openstax, R.U. 1.1 The Science of Biology. Available online: http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introduction (accessed on 2021).

Quizlet. 2.1.5 Biological Membranes. Available online: https://quizlet.com/gb/377924943/215-biological-membranes-diagram/ (accessed on 2021).

Seydel, J.K.; Wiese, M. Drug-Membrane Interactions: Analysis, Drug Distribution, Modeling; John Wiley & Sons: Hoboken, NJ, USA, 2009; Volume 15.

Gillette, J.R. Factors affecting drug metabolism. Ann. N. Y. Acad. Sci. 1971, 179, 43–66. DOI: https://doi.org/10.1111/j.1749-6632.1971.tb46890.x

Ekins, S.; Ring, B.J.; Grace, J.; McRobie-Belle, D.J.; Wrighton, S.A. Present and future in vitro approaches for drug metabolism. J. Pharmacol. Toxicol. Methods 2000, 44, 313–324. DOI: https://doi.org/10.1016/S1056-8719(00)00110-6

Taft, D.R. Drug excretion. In Pharmacology; Elsevier: Amsterdam, The Netherlands, 2009; pp. 175–199. DOI: https://doi.org/10.1016/B978-0-12-369521-5.00009-9

Reinberg, A.E. Concepts of circadian chronopharmacology. Ann. N. Y. Acad. Sci. 1991, 618, 102–115. DOI: https://doi.org/10.1111/j.1749-6632.1991.tb27239.x

Prabu, S.L.; Suriyaprakash, T.; Ruckmani, K.; Thirumurugan, R. Biopharmaceutics and Pharmacokinetics. In Basic Pharmacokinetic Concepts and Some Clinical Applications; IntechOpen: London, UK, 2015. DOI: https://doi.org/10.5772/61160

Hallare, J.; Gerriets, V. Half Life; StatPearls Publishing LLC: Treasure Island, FL, USA, 2020.

Hardenia, A.; Maheshwari, N.; Hardenia, S.S.; Dwivedi, S.K.; Maheshwari, R.; Tekade, R.K. Scientific rationale for designing controlled drug delivery systems. In Basic Fundamentals of Drug Delivery; Elsevier: Amsterdam, The Netherlands, 2019; pp. 1–28 DOI: https://doi.org/10.1016/B978-0-12-817909-3.00001-7

Paarakh, M.P.; Jose, P.A.; Setty, C.; Christoper, G.P. Release kinetics–concepts and applications. Int. J. Pharm. Res. Technol. 2018, 8, 12–20.

Habet, S. Narrow Therapeutic Index drugs: Clinical pharmacology perspective. J. Pharm. Pharmacol. 2021, 73, 1285–1291. DOI: https://doi.org/10.1093/jpp/rgab102

Lowe, E.S.; BALIS, F.M. Dose-effect and concentration-effect analysis. In Principles of Clinical Pharmacology; Elsevier: Amsterdam, The Netherlands, 2007; pp. 289–300. [ DOI: https://doi.org/10.1016/B978-012369417-1/50058-4

Park, K. Controlled drug delivery systems: Past forward and future back. J. Control. Release 2014, 190, 3–8. DOI: https://doi.org/10.1016/j.jconrel.2014.03.054

Fenton, O.S.; Olafson, K.N.; Pillai, P.S.; Mitchell, M.J.; Langer, R. Advances in biomaterials for drug delivery. Adv. Mater. 2018, 30, 1705328. DOI: https://doi.org/10.1002/adma.201705328

Singh, A.P.; Biswas, A.; Shukla, A.; Maiti, P. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduct. Target. Ther. 2019, 4, 1–21. DOI: https://doi.org/10.1038/s41392-019-0068-3

Mitragotri, S.; Burke, P.A.; Langer, R. Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nat. Rev. Drug Discov. 2014, 13, 655–672. DOI: https://doi.org/10.1038/nrd4363

Gupta, B.P.; Thakur, N.; Jain, N.P.; Banweer, J.; Jain, S. Osmotically controlled drug delivery system with associated drugs. J. Pharm. Pharm. Sci. 2010, 13, 571–588. DOI: https://doi.org/10.18433/J38W25

Wang, Z.; Shmeis, R.A. Dissolution controlled drug delivery systems. Des. Control. Release Drug Deliv. Systems. 2006, 139–172.

Siepmann, J.; Siegel, R.A.; Siepmann, F. Diffusion controlled drug delivery systems. In Fundamentals and Applications of Controlled Release Drug Delivery; Springer: Berlin/Heidelberg, Germany, 2012; pp. 127–152. DOI: https://doi.org/10.1007/978-1-4614-0881-9_6

Siepmann, J.; Siepmann, F. Modeling of diffusion controlled drug delivery. J. Control. Release 2012, 161, 351–362. DOI: https://doi.org/10.1016/j.jconrel.2011.10.006

Srikonda, S.; Kotamraj, P.; Barclay, B. Osmotic controlled drug delivery systems. Des. Control. Release Drug Deliv. Syst. 2006, 1, 203.

Patil, P.B.; Uphade, K.B.; Saudagar, R.B. A review: Osmotic drug delivery system. Pharma Sci. Monit. 2018, 9, 2.

Kumar, P.; Mishra, B. An overview of recent patents on oral osmotic drug delivery systems. Recent Pat. Drug Deliv. Formul. 2007, 1, 236–255. DOI: https://doi.org/10.2174/187221107782331638

Pfizer Laboratories Div Pfizer Inc. Procardia XL. Osmotic Pump. Available online: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06

Sudafed Osmotic Pump. Available online: https://www.sudafed.com/products/sudafed-sinus-congestion

Inc., B. Viadur (Leuprolide Acetate Implantable Osmotic Pump). Available online: http://usrf.org/breakingnews/viadur_implant.html

Siepmann, J.; Siepmann, F. Swelling controlled drug delivery systems. In Fundamentals and Applications of Controlled Release Drug Delivery; Springer: Berlin/Heidelberg, Germany, 2012; pp. 153–170. DOI: https://doi.org/10.1007/978-1-4614-0881-9_7

Kopeček, J. Polymer–drug conjugates: Origins, progress to date and future directions. Adv. Drug Deliv. Rev. 2013, 65, 49–59. DOI: https://doi.org/10.1016/j.addr.2012.10.014

Yun, Y.H.; Lee, B.K.; Park, K. Controlled drug delivery: Historical perspective for the next generation. J. Control. Release 2015, 219, 2–7. DOI: https://doi.org/10.1016/j.jconrel.2015.10.005

Guo, M.X. Dissolution Testing: In Vitro Characterization of Oral Controlled Release Dosage Forms; Wiley: Hoboken, NJ, USA, 2010. DOI: https://doi.org/10.1002/9780470640487.ch15

Adeosun, S.O.; Ilomuanya, M.O.; Gbenebor, O.P.; Dada, M.O.; Odili, C.C. Biomaterials for Drug Delivery: Sources, Classification, Synthesis, Processing, and Applications. In Advanced Functional Materials; IntechOpen: London, UK, 2020.