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COMPLEX DRUG DELIVERY SYSTEMS

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COMPLEX DRUG DELIVERY SYSTEMS

Rahul Raghav Dasari, Chinthaginjala Haranath * and Hindustan Abdul Ahad

Department of Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), KR Palli Cross, Chiyyedu (PO), Anantapur, Andhra Pradesh, India.

ABSTRACT: The majority of current drug delivery systems are existed as water-insoluble drug delivery systems but rarely water-soluble drug delivery systems. Low aqueous solubility is a common problem in pharmaceutical development. About 40% of commercialized drugs and as many as 90% of drugs in the discovery are low aqueous soluble. When given through traditional dosage forms, such drugs fail to be soluble and have limited bioavailability, so they tend to show limited therapeutic effect and often fail. Various methods to solubilize drugs usually involve a combination of pH modifiers, salt forms, co-solvent systems, surfactants, or complexation. A complex drug system is generally a complex system incorporated with API and compatible excipients to produce the desired effect. Complex drug systems are simply referred to as uncommon products that were not typical tablets. However, with the rise of insoluble API biologics, complex drug systems are quickly gaining importance. Most used complexes include phosphor lipid complex, chitosan complex, cyclodextrins complex, phosphatidylcholine complex. Complex drug systems are employed in various areas for treating various clinical conditions like insulin complexes for antidiabetic treatment, platinum complexes for anticancer treatment, cyclodextrins complexes for schizophrenia. They are developed by solubilization & bioavailability enhancement techniques, drug-eluting systems, sterile products, highly potent API or controlled substances.

Keywords: Complex drug delivery systems (CDS), Solubility, Phospholipid complex, Chitosan complex, Cyclodextrins complex, Phosphatidylcholine complex

INTRODUCTION: Drug delivery is the technique of regulating a drug to achieve a therapeutic effect in people. Drug substances such as fuse liposomes, proliposomes, microspheres, gels, cyclodextrins,

prodrugs among others, have significant advantages over conventional dosage forms 1. There might be a consistent, controlled, or focused drug delivery with this kind of system.

As per clinical application, various drugs are being controlled through different conventional drug delivery dose structures such as solutions, lotions, mixtures, creams, gels, balms, powders, suppositories, suspensions, injectables, pills, immediate-release capsules, and tablets, etc. to treat unique infections. Development of new devices with improved potential incorporate oral controlled delivery, fast dispersing dose structures, liposomes, taste-markers, transdermal patches, and site-specific delivery systems 2. A newly emerging approach was developed based on the combination of phosphor lipid complexation and micelle techniques to enhance the oral antidiabetic effect of repaglinide (RG), Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method 3. The concept of employing electrospun nanofibers as a matrix and improving hydrophobic compounds' solubility by combining drug/CD-IC and versatile electrospinning process 4. Platinum (IV) complex has the striking advantage of the functional modification of the axial ligands for improved physicochemical properties and pharmacokinetic profiles. Many promising achievements were obtained in the field of Pt (IV) complex-based nano delivery systems. However, the limitations such as safety of the nanocarriers and scale-up production may impede Pt (IV) complex-based nanomedicines translation into clinical studies for stimuli-triggered drug release, ligand-mediated targeting, and combinational drug therapy 5. The article focuses on the classification, ability of various complexes to enhance drug release at targeted sites and their applications. Complex Drug Systems have become so prevalent that the FDA has defined them with the following categories as mentioned in Table 1.

TABLE 1: FDA CLASSIFICATION OF COMPLEX SYSTEMS

Classification Examples
Complex Active Ingredients Peptides, polymeric compounds
Complex formulations liposomes, colloids.
Complex routes of delivery

 

 Locally acting drugs, ophthalmological products such as suspensions, emulsions, or gels.
Complex dosage forms Implantable, transdermal, metered-dose inhalers, extended-release injectable
Complex drug-device combination products Auto-injectors6.

Complex Active Ingredients API: Every drug product contains API, irrespective of its route and dosage form. Newer drugs are difficult to obtain frequently by simple approaches, as traditional solid oral dosage forms. This usually causes problems related to the bioavailability of dosage forms, particularly for BCS-II oral drugs. In 2017, there were 63 drug product grants to 505(b) (2) regulatory pathways, an all-time high. This route of approval has become of significant importance over the last decade and usually involves innovative dosage forms or drug delivery methods that are considered complex. These results in increased compliance, improve patient outcomes and provide additional economic opportunities for their sponsors, but they are considered as complex Drug Systems due to the following criteria

  • Challenges in scale-up
  • Less defined regulatory pathway
  • Complex formulation and excipients
  • Complicated characterizations
  • No standard in-vitro drug release assay
  • Few models correlating in-vitro drug release with in-vivo pharmacokinetic 7.

Complex Dosage Forms: Any non-oral complex dose structure has regularly at least two discrete matters inside the formulation. There are various methods available to increase the solubility of drugs and improve their delivery, including particle size reduction, micronization and nano milling, and amorphous solid dispersions, namely hot melt extrusion or spray drying processes. Encapsulation methods include Solid lipid Particles, liposomes, and reverse cubic phase particles.

Complex Drug Devices: In this type, the drug constituent part is pre-stacked in a device, in which the device configuration influences drug delivery to the site of absorption. Drug-eluting systems (DES) are combinations of drugs and polymer wherein the polymer acts as a vehicle to deliver the drug. There are two categories of drug-eluting systems Table 2.

TABLE 2: TYPES OF DRUG-ELUTING SYSTEMS

Biodegradable DES (bio absorbable) Bio durable drug-eluting devices
Use biocompatible materials such as Poly Lactic-co-Glycolic Acid (PLGA) to deliver drugs that decompose in the body over time. Use biocompatible materials like silicone, polyethylene-vinyl acetate, and thermoplastic polyurethane (TPU) to deliver drugs. Bio durable drug-eluting devices can be designed as a matrix, reservoir, or osmotic systems to deliver drugs via diffusion or osmosis 8.

Complex Transdermal Systems: These are commonly intended to convey an API through the skin for systemic activity. The saturation of an API through the skin is constrained by changing drug concentration and preparation composition 9. A bilayer drug in adhesive TDDS configuration may permit improved permeation of the drug release by fluctuating layer thicknesses and drug spatial circulation over each layer 10. Table 3. illustrates the previous research work done by various researchers using a specific complex and the API and excipients used to develop an intended complex drug delivery system.

TABLE 3: PAST WORK DONE ON THE COMPLEX DRUG DELIVERY SYSTEM

S. no. Drug Name Excipients used Complex Reference
1 Amphotericin B 4-arm-PEG10,000-MAL Amphotericin B (AmB) Coumarin-6 (C6) 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindotricarbo cyanine iodide (DiR). Rabbit anti-SPARC antibody micro-to-nano (MTN) albumin Complex 11
2 Doxycycline Hydrochloride Transcutol Hp, Poloxamer 188 And Cremophor Rh40 Peceol, Labrasol, Labrafac Lipophile Wl1349 Polysaccharide 12
3 amlodipine besylate β-Cyclodextrin,

Peg- Kolliphor Ps20, Polysorbate 20 (Ps20), And Kolliphor P188, Poloxamer 188.

 β-Cyclodextrin

Inclusion complexes

 13
4 Thiram HPMC β-CyclodextrinThiram, Dimethyl Sulfoxide, Triethylamine, Sodium Chloride hydroxypropyl-C inclusion complex 14
5 Folic acid Lignin, Ethanol, Sodium Hydroxide, Sulfuric Acid. Sodium Dodecyl Benzenesulfonate, 3-Chloro-2 Hydroxypropyltrimethylammonium Chloride, Platinum Complex 15
6 5 – Fluro Uracil Berberine,

Ethanol, Formic Acid, Methanol & Acetonitrile.

 Hydrogel Complex 16
7 Boron Nitride Boron Nitride, Poloxamer 188 (P188), Poly (Ethylene Glycol), Poly (Propylene Glycol), Poly (Ethylene Glycol), Dichloromethane, Ethyl Alcohol Nanocarriers 17
8 Eudragit® SpioNanoparticles, Phosphate-Buffered Saline (Pbs), Nitric Acid, HCL Interpolyelectrolyte complexes 18
9 Domperidone Domperidone, Sodium Polystyrene Sulfonate, Dodecyl Trimethyl Ammonium Bromide Domperidone resinate complex 19
10 Tetracycline Tetracycline, anionic beta-cyclodextrin complex, Sulfisoxazole, Ethanol, Acetonitrile, Methanol, anionic beta-cyclodextrin complex 20
11 Ruthenium Polyethylene Glycol,Poly (Glutamic Acid), Poly(L-Lysine),

Methoxylpoly(Ethylene Glycol).

 polypyridyl complexes 21
10 ferulic acid Cyclodextrins, Cellulose, Sulphuric Acid, Glycidyltrimethyl Ammonium Chloride, Β-Cyclodextrin cyclodextrin inclusion complex 22
13 5-fluorouracil Chitosan, Acetone, Ether, Methanol, Ethanol, Pyridine, Dmso Chitosanaptamer complex 23
14 Insulin Insulin, phosphatidylcholine, Deoxynucleotidyl Transferase, Poly (ADP-Ribose) Polymerase. phosphatidylcholine complex 24
15 Ibuprofen Ibuprofen, Sulfisoxazole, Ethanol, Acetonitrile, Methanol, Lysozyme Polyelectrolyte–surfactant–complex 25
16 Supramolecules (DNA) Chitosan, phosphatidylcholine, Deoxynucleotidyl Transferase, Poly (ADP-Ribose) Polymerase Chitosan Complex 26
17 Chitosan-N-acetylcysteine Chitosan, acetylcysteineTriethylamine,

Tetrahydrofuran, Dichloromethane

 HP-β-CD inclusion complex 27
18 carboxymethyl starch (CMS) and chitosan (Cs) Capryol 90, Labrafac Cc, Labrasol, Lauroglycol, Oleic Acid, Tween 80, Tween 20, Span 20, Propylene Glycol, Peg 400 And Peg 200 polyelectrolyte complex 28
19 Domperidone Domperidone, Simvastatin, Filipin, 1, 6-Diphenyl-1, 3, 5-Hexatriene, Nile Red, Verapamil, Fetal Bovine Serum resinate complex 29
20 chitosan Calcium hydride, PEG, Methyl Ether, Tetrahydrofuran, Fluorescein Isothiocyanate polyelectrolyte complexes 30
21 Metronidazole Metronidazole, Hydroxypropyl-β-Cyclodextrin, Monomethyl Ether, Γ-Benzyl-L-Glutamate-N-Carboxyanhydride (Blg-Nca)  Dimethylformamide Hydroxypropyl-β-Cyclodextrin inclusion complex 31
22 paclitaxel Paclitaxel, Sodium Hydroxide, Glacial Acetic Acid, Sodium Acetate, Sodium Starch Glycolate (SSG), Potassium Dihydrogen Phosphate, Magnesium Stearate, Talc phospholipid complex 32
23 Curcumin Acetone, Paraformaldehyde, Xylene, Toluene, Ether, Ethanol, P-Tert-Butylphenol, Phenol, Sodium Hydroxide, Barium Carbonate, Aluminum Trichloride, Concentrated H2so4 &Hcl, Phosphate Buffered Saline pH 7.4 lecithin complex 33
24 indomethacin High Amylose Starch (HylonVii), Lecithin, Glyceryl Tristearate, Carboxymethylcellulose, Ethyl Cellulose, Mesalamine phospholipid complex 34
25 Doxorubicin hydrochloride 6-Deoxy-6-[(2-Aminoethyl) Amino]-Β-Cyclodextrin, Folic Acid,

N-Hydroxysuccinimide, Carboxymethylcellulose, Xanthan, Pectin, Alginate

 DOX-MSN-ZnO-PLL-PLL(DMA) 35
26 iridium Polyethylene Glycol, Poly (Glutamic Acid), Poly(L-Lysine),

Methoxylpoly(Ethylene Glycol).

 polypyridyl complexes 36
27 benznidazole Polyethylene Glycol, Poly (Glutamic Acid), Cellulose, Sulphuric Acid, Glycidyltrimethyl Ammonium Chloride, Β-Cyclodextrin polymethacrylate interpolyelectrolyte complexes 37
2 clindamycin phosphate Polyethylene Glycol, Poly (Glutamic Acid), Poly(L-Lysine),

Methoxylpoly(Ethylene Glycol),  Acetone, Ether, Methanol, Ethanol, Pyridine, Dmso.

 polyelectrolyte complex 38
8 Atenolol Atenolol, β-cyclodextrin,Deoxynucleotidyl Transferase, Poly (ADP-Ribose) Polymerase β-cyclodextrin 39
29 Lidocaine Lidocaine, β-cyclodextrinRibonuclease A, Trypsin, Thrombin, N-Hydroxysuccinimide, Lysozyme. β-cyclodextrin 40
30 chlorthalidone Soluplus, chlorthalidone, sodium lauryl sulfate Methoxylpoly(Ethylene Glycol) Soluplus-sodium lauryl sulfate complex 41
31 Titanium Dioxide ruthenium, Cellulose, TiO2, Sulphuric Acid, Glycidyltrimethyl Ammonium Chloride, ruthenium complex 42
32 methotrexate &cyclophosphamide methotrexate &cyclophosphamide, N-Hydroxysuccinimide, Dicyclohexyl Carbodiimide, Acetone, Ether, Methanol, Ethanol, Pyridine, Dmso Interpolymer complex 43
33 Indomethacin- Eudragit® Indomethacin, Eudragit, Deoxynucleotidyl Transferase, Poly (ADP-Ribose) Polymerase. Interpolyelectrolyte complexes 44
34 hyaluronan Poly-4-Phenylene Tetraiodide (PFEP), Sodium Hyaluronate, Hyaluronidase, Ribonuclease A, Trypsin, Thrombin, N-Hydroxysuccinimide, Lysozyme. polysaccharide complexes 45
35 Rhenacarborane Polyethylene Glycol, Poly (Glutamic Acid), Poly(L-Lysine), rhenacarborane

Methoxylpoly(Ethylene Glycol)

 rhenacarborane complexes 46
36 Breviscapine Polyethylene Glycol, Poly (Glutamic Acid), Poly(L-Lysine), Cellulose, Sulphuric Acid Polyelectrolyte- ionic complexes 47
37 Oxaprozin Oxaprozin,

N-Hydroxysuccinimide, Dicyclohexyl Carbodiimide, Acetone, Ether, Methanol, Ethanol, Pyridine, Dmso

 hydrogels and nickel complex 48
38 folic acid Cyclodextrins, Folic AcidCellulose, Sulphuric Acid, Glycidyltrimethyl Ammonium Chloride, Β-Cyclodextrin cyclodextrin complex 49

Marketed products of the complex drug delivery systems were represented in Table 4.

TABLE 4: MARKETED COMPLEX DRUG PRODUCTS

Ozurdex®

NuvaRing®

Zuplenz®

Narcan®

Avycaz®

Bendeka™

Omnitrope®

Yosprala™

Lupron Depot®,

Xuriden™

CONCLUSION: The literature search unquestionably ratifies the progressively increasing popularity of complex drug systems in designing formulations.

A variable number of complexes were seen in the drug industry, where they are applied much more frequently. Only a min fraction of industrial studies were reported and most investigations remain as only in-house information.

The supervision and control of new complex system development help in product improvement.

TABLE 5: APPLICATIONS OF COMPLEX DRUG DELIVERY

S. no. Complex Application
1 Hydrogel PEG PA-PEG Tissue engineering. Live cell biosensor. Glucose biosensor 50
2 PLGA/PVA complex gel Temperature-sensitive polymer system for drug delivery 51
3 polyelectrolyte complex Carrier for colon-specific drug delivery 52
4 cyclodextrin-naproxen inclusion complex Enhanced solubility and permeation of poorly water-soluble drugs53.

 
5 lidocaine (LC) and β cyclodextrin (β-CD) inclusion complex Improve the drug safety and enhance the penetration and release of the drug54.
6 morin-phospholipid complex Enhance oral bioavailability+42
7 Rosin Cyclodextrin Complexes AS film-forming materials to achieve controlled drug release. Matrix-forming material to achieve sustained drug release. AS for taste masking agents in oral drug delivery 55
8 Chitosan Complex Enhances the residence time of the system and consequently the bioavailability of the drug 56
9 Polyelectrolyte Complex Controlled Loading and Improved Release performance for Bone Therapeutics
10 lignin-based complex micelles Used for pH drug dependence 57

ACKNOWLEDGMENT: The authors are thankful to the Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapur, for providing facilities.

CONFLICTS OF INTEREST: The author declares no conflict of interest.

REFERENCES:

  1. Bandawane A and Saudagar R: A review on novel drug delivery system: a recent trend. Journal of Drug Delivery and Therapeutics 2019; 9(3): 517-21.
  2. Nayak AK, Ahmad SA, Beg S, Ara TJ and Hasnain MS: Drug delivery: present, past and future of medicine. In Applications of Nanocomposite Materials in Drug Delivery 2018; 1: 255-82.
  3. Kassem AA, Abd El-Alim SH, Basha M and Salama A: Phospholipid complex enriched micelles: a novel drug delivery approach for promoting the antidiabetic effect of repaglinide. European Journal of Pharmaceutical Sciences 2017; 99: 75-84.
  4. Aytac Z, Sen HS, Durgun E and Uyar T: Sulfisoxazole/cyclodextrin inclusion complex incorporated in electrospun hydroxypropyl cellulose nanofibers as drug delivery system. Colloids and Surfaces B Biointerfaces 2015; 128: 331-38.
  5. Han X, Sun J, Wang Y and He Z: Recent advances in platinum (IV) complex‐based delivery systems to improve platinum (II) anticancer therapy. Medicinal Research Reviews 2015; 35(6): 1268-99.
  6. Vyas A, Saraf S and Saraf S: Cyclodextrin based novel drug delivery systems. Journal of Inclusion Phenomena and Macrocyclic Chemistry 2008; 62(1-2): 23-42.
  7. Berger R: Innovation for generic drugs: science and research under the generic drug user fee amendments of 2012. Clinical Therapeutics & Pharmacology 2019; 105(4): 880-85.
  8. Lion R: Innovation for generic drugs: science and research under the generic drug user fee amendments of 2012. Clinical Pharmacology & Therapeutics 2019; 105(4): 875-80.
  9. Lionberger R: Innovation for generic drugs: science and research under the generic drug user fee amendments of 2012. Clinical Pharmacology & Therapeutics 2019; 105(4): 878-85.
  10. Davis DA, Martins PP, Zamloot MS, Kucera SA, Williams III RO, Smyth HD and Warnken ZN: Complex drug delivery systems: controlling transdermal permeation rates with multiple active pharmaceutical ingredients. AAPS Pharm Sci Tech 2020; 21: 165.
  11. Cheng L, Niu MM, Yan T, Ma Z, Huang K, Yang L, Zhong X, Li C. Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections. Acta Pharmaceutica Sinica B. 2021; 8-15.
  12. Chen C, Wang Y, Zhang D, Wu X, Zhao Y, Shang L, Ren J and Zhao Y: Natural polysaccharide-based complex drug delivery system from microfluidic electrospray for wound healing. Applied Materials Today 2021; 1(1): 1-10.
  13. Jindal R: RSM-CCD optimized microwave-assisted synthesis of chitosan and sodium alginate-based nanocomposite containing inclusion complexes of β-cyclodextrin and amlodipine besylate for sustained drug delivery systems. Journal of Drug Delivery Science and Technology 2021; 61: 1023-25.
  14. Gao S, Liu Y, Jiang J, Li X, Ye F, Fu Y and Zhao L: Thiram/hydroxypropyl-β-cyclodextrin inclusion complex electrospun nanofibers for a fast-dissolving water-based drug delivery system. Colloids and Surfaces B Biointerfaces 2021; 201: 116-25.
  15. He C, Majd MH, Shiri F and Shahraki S: Palladium and platinum complexes of folic acid as new drug delivery systems for treatment of breast cancer cells. Journal of Molecular Structure 2021; 1(2): 129-35.
  16. Xiao Y, Gu Y, Qin L, Chen L, Chen X, Cui W, Li F, Xiang N and He X: Injectable thermosensitive hydro gel-based drug delivery system for local cancer therapy. Colloids and Surfaces B Biointerfaces 2021; 1(2): 111-18.
  17. Tu X, Xu H, Li C, Liu X, Fan G and Sun W: Adsorption performance of boron nitride nanomaterials as effective drug delivery carriers for anticancer drugs based on density functional theory. Computational and Theoretical Chemistry 2021; 1(2): 113-19.
  18. Porfiryeva NN, Semina II, Salakhov IA, Moustafine RI and Khutoryanskiy VV: Mucoadhesive and mucus-penetrating Inter polyelectrolyte complexes for nose-to-brain drug delivery. nanomedicine: Nanotechnology, Biology and Medicine 2021; 1(2): 1024-29.
  19. Daihom BA, Bendas ER, Mohamed MI and Badawi AA: Domperidone resinate complex as a new formulation for gastroretentive drug delivery. Journal of Drug Delivery Science and Technology 2020; 58: 101-08.
  20. Verza BS, van den Becken JJ, Brandt JV, Junior MJ, Barao VA, Piazza RD, Tagit O, Spolidorio DM, Vergani CE and de Avila ED: A long-term controlled drug-delivery with anionic beta-cyclodextrin complex in layer-by-layer coating for percutaneous implants devices. Carbohydrate Polymers 2021; 257: 117-21.
  21. Shi H, Lou J, Lin S, Wang Y, Hu Y, Zhang P, Liu Y and Zhang Q: Diatom-like silica–protein nanocomposites for sustained drug delivery of ruthenium polypyridyl complexes. Journal of Inorganic Biochemistry 2021; 221: 111-14.
  22. Celebioglu A and Uyar T: Development of ferulic acid/cyclodextrin inclusion complex nanofibers for fast-dissolving drug delivery system. International Journal of Pharmaceutics 2020; 584: 119-25.
  23. Zavareh HS, Pourmadadi M, Moradi A, Yazdian F and Omidi M: Chitosan/carbon quantum dot/aptamer complex as a potential anticancer drug delivery system towards the release of 5-fluorouracil. International Journal of Biological Macromolecules 2020; 165: 1422-30.
  24. Bravo-Alfaro DA, Muñoz-Correa MO, Santos-Luna D, Toro-Vazquez JF, Cano-Sarmiento C, García-Varela R and García HS: Encapsulation of an insulin-modified phosphatidylcholine complex in a self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery. Journal of Drug Delivery Science and Technology 2020; 57: 1016-22.
  25. Mirtic J, Paudel A, Laggner P, Hudoklin S, Kreft ME and Kristl J: Polyelectrolyte–surfactant–complex nanoparticles as a delivery platform for poorly soluble drugs: A case study of ibuprofen loaded cetylpyridinium-alginate system. International Journal of Pharmaceutics 2020; 580: 19-124.
  26. Pakornpadungsit P, Prasopdee T, Swainson NM, Chworos A and Smitthipong W: DNA: chitosan complex, known as a drug delivery system, can create a porous scaffold. Polymer Testing 2020; 83: 106-12.
  27. Lan Q, Di D, Wang S, Zhao Q, Gao Y, Chang D and Jiang T: Chitosan-N-acetylcysteine modified HP-β-CD inclusion complex as a potential ocular delivery system for an anti-cataract drug: Quercetin. Journal of Drug Delivery Science and Technology 2020; 55: 1014-20.
  28. Quadrado RF and Fajardo AR: Microparticles based on carboxymethyl starch/chitosan polyelectrolyte complex as vehicles for drug delivery systems. Arabian Journal of Chemistry 2020; 13(1): 2183-94.
  29. Daihom BA, Bendas ER, Mohamed MI and Badawi AA: Domperidone resinate complex as a new formulation for gastroretentive drug delivery. Journal of Drug Delivery Science and Technology 2020; 58: 1018-24.
  30. Potas J, Szymańska E and Winnicka KL: Challenges in developing chitosan-based polyelectrolyte complexes as a platform for mucosal and skin drug delivery. European Polymer Journal 2020; 6(1): 110-20.
  31. Celebioglu A and Uyar T: Metronidazole/Hydroxypropyl-β-Cyclodextrin inclusion complex nanofibrous webs as fast-dissolving oral drug delivery system. International Journal of Pharmaceutics 2019; 572: 118-28.
  32. Ding D, Sun B, Cui W, Chen Q, Zhang X, Zhang H, He Z, Sun J and Luo C: Integration of the phospholipid-drug complex into self-nanoemulsifying drug delivery system to facilitate oral delivery of paclitaxel. Asian Journal of Pharmaceutical Sciences 2019; 14(5): 552-58.
  33. Kathpalia H, Salunkhe S and Juvekar S: Formulation of gastroretentive sustained release floating in situ gelling drug delivery system of solubility enhanced curcumin-soy lecithin complex. Journal of Drug Delivery Science and Technology 2019; 53: 1012-19.
  34. Kaffash E, Badiee A, Akhgari A, Rezayat NA, Abbaspour M and Saremnejad F: Development and characterization of a multi particulate drug delivery system containing indomethacin-phospholipid complex to improve dissolution rate. Journal of Drug Delivery Science and Technology 2019; 53: 101-07.
  35. Kuang Y, Chen H, Chen Z, Wan L, Liu J, Xu Z, Chen X, Jiang B and Li C: Poly (amino acid)/ZnO/mesoporous silica nanoparticle-based complex drug delivery system with a charge-reversal property for cancer therapy. Colloids and Surfaces B Biointerfaces 2019; 181(1): 461-69.
  36. Zhang WY, Du F, He M, Bai L, Gu YY, Yang LL and Liu YJ: Studies of anticancer activity in-vitro and in vivo of iridium (III) polypyridyl complexes-loaded liposomes as drug delivery system. European Journal of Medicinal Chemistry 2019; 178(1): 390-400.
  37. García MC, Martinelli M, Ponce NE, Sanmarco LM, Aoki MP, Manzo RH and Jimenez-Kairuz AF: Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes. European Journal of Pharmaceutical Sciences 2018; 120: 107-22.
  38. Kilicarslan M, Ilhan M, Inal O and Orhan K: Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy. European Journal of Pharmaceutical Sciences 2018; 123(1): 441-51.
  39. Kaur K, Jindal R and Jindal D: RSM-CCD optimized microwave-assisted synthesis of chitosan and gelatin-based pH-sensitive, inclusion complexes incorporated hydro gels and their use as controlled drug delivery systems. Journal of Drug Delivery Science and Technology 2018; 48(2): 161-73.
  40. Abou-Okeil A, Rehan M, El-Sawy SM, El-Bisi MK, Ahmed-Farid OA and Abdel-Mohdy FA: Lidocaine/β-cyclodextrin inclusion complex as drug delivery system. European Polymer Journal 2018; 108(1): 304-30.
  41. Franca MT, Pereira RN, Riekes MK, Pinto JM and Stulzer HK: Investigation of novel supersaturating drug delivery systems of chlorthalidone: The use of the polymer-surfactant complex as an effective carrier in solid dispersions. European Journal of Pharmaceutical Sciences 2018; 111(1): 142-52.
  42. Nesic M, Zakula J, Koricanac L, Stepic M, Radoicic M, Popovic I, SaponjiS Z and Petkovic M: Light controlled metallodrugs delivery system based on the TiO2-nanoparticles and Ru-complex. Journal of photochemistry and Photobiology A Chemistry 2017; 347: 55-66.
  43. Azqhandi MH, Farahani BV and Dehghani N: Encapsulation of methotrexate and cyclophosphamide in interpolymer complexes formed between polyacrylic acid and polyethylene glycol on multi-walled carbon nanotubes as drug delivery systems. Materials Science and Engineering 2017; 79(1): 841-47.
  44. Moustafine RI, Sitenkov AY, Bukhovets AV, Nasibullin SF, Appeltans B, Kabanova TV, Khutoryanskiy VV and Van den Mooter G: Indomethacin-containing inter polyelectrolyte complexes based on Eudragit® E PO/S 100 copolymers as a novel drug delivery system. International J of Pharmaceutics 2017; 524(12): 121-33.
  45. Wu D, Encinas A, Verrier B, Cuvillier A, Champier G, Paul S and Delair T: Ternary polysaccharide complexes: colloidal drug delivery systems stabilized in physiological media. Carbohydrate Polymers 2017; 172: 265-74.
  46. Pruitt DG, Bullock KM, Banks WA, Jelliss PA. Development of rhenacarborane complexes as central nervous system (CNS) drug delivery agents. Inorganica Chimica Acta. 2017; 466:139-44.
  47. Olivera ME, Manzo RH, Alovero F, Jimenez-Kairuz AF, Ramírez-Rigo MV. Polyelectrolyte-drug ionic complexes as nanostructured drug carriers to design solid and liquid oral delivery systems. Nanostructures for Oral Medicine 2017; 1(2): 365-08.
  48. Babic MM, Bozic BĐ, Filipovic JM, Uscumlic GS and Tomic SL: Evaluation of novel antiproliferative controlled drug delivery system based on poly (2-hydroxypropyl acrylate/itaconic acid) hydrogels and nickel complex with Oxaprozin. Materials Letters 2016; 163(2): 214-17.
  49. Xu J, Xu B, Shou D, Qin F, Xu Y and Hu Y: Characterization and evaluation of a folic acid receptor-targeted cyclodextrin complex as an anticancer drug delivery system. European Journal of Pharmaceutical Sciences 2016; 83(1): 132-42.
  50. Said AE: Radiation synthesis of inter polymer polyelectrolyte complex and its application as a carrier for colon-specific drug delivery system. Biomaterials 2005; 26(15): 2733-39.
  51. Canbolat MF, Celebioglu A and Uyar T: Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers. Colloids and Surfaces B Biointerfaces 2014; 115(1): 15-21.
  52. Abou-Okeil A, Rehan M, El-Sawy SM, El-Bisi MK, Ahmed-Farid OA and Abdel-Mohdy FA: Lidocaine/β-cyclodextrin inclusion complex as drug delivery system. European Polymer Journal 2018; 108(2): 304-10.
  53. Zhang J, Peng Q, Shi S, Zhang Q, Sun X, Gong T and Zhang Z: Preparation, characterization and in-vivo evaluation of a self-nano emulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex. International Journal of Nanomedicine 2011; 6(2): 3405-10.
  54. Yadav BK, Gidwani B and Vyas A: Rosin: recent advances and potential applications in novel drug delivery system. Journal of Bioactive and Compatible Polymers 2016; 31(2): 111-26.
  55. Saikia C, Gogoi P and Maji TK: Chitosan: A promising biopolymer in drug delivery applications. J Mol Genet Med S 2015; 4(006): 899-10.
  56. Vehlow D, Schmidt R, Gebert A, Siebert M, Lips KS and Müller M: Polyelectrolyte complex based interfacial drug delivery system with controlled loading and improved release performance for bone therapeutics. Nanomaterials 2016; 6(3): 53.
  57. Li Y, Qiu X, Qian Y, Xiong W and Yang D: pH-responsive lignin-based complex micelles: Preparation, characterization, and application in oral drug delivery. Chemical Engineering Journal 2017; 327: 1176-83.

    How to cite this article:

    Dasari RR, Haranath C and Abdul HA: Complex drug delivery systems. Int J Pharm Sci & Res 2022; 13(4): 1533-39. doi: 10.13040/IJPSR.0975-8232.13(4). 1533-39

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English

IJPSR

Rahul Raghav Dasari, Chinthaginjala Haranath * and Hindustan Abdul Ahad

Department of Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), KR Palli Cross, Chiyyedu (PO), Anantapur, Andhra Pradesh, India.

haranathriper@gmail.com

13 June 2021

23 July 2021

25 July 2021

10.13040/IJPSR.0975-8232.13(4).1533-39

01 April 2022

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