Abstract
Introduction: Nanocrystals constitutes of 100% drug and considered as a “new drug” by Food and Drug Administration. It is proven to be an effective alternative for topical delivery of drug with increased bioavailability. Recently formulation of the drug as nanocrystals has been accomplished for many drugs exhibiting low aqueous solubility, ineffective permeability or both in order to increase the dermal bioavailability.
Conclusion: In this review article, an effort was made to explain the role of nanocrystals in the dermal delivery of the drug which results in increased bioavailability and efficacy through enhancement of solubility, dissolution velocity, permeation and penetration. Recently dermal delivery of the drug as nanocrystals is a challenging method but explained by many researchers through their work. Preparation of drugs as nanocrystals might be a promising method of drug delivery to Class II and Class IV drugs of Biopharmaceutical Classification System. Drug nanocrystals can also be applied in cosmetics for effective results.
Keywords: Saturation solubility, increased dissolution, improved penetration, enhanced bioavailability, dermal delivery, nanocrystals.
Graphical Abstract
[1]
Teixeira, M.C.; Carbone, C.; Souto, E.B. Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery. Prog. Lipid Res., 2017, 68, 1-11.
[2]
Borchard, G. Drug nanocrystals.In: Non-Biological Complex Drugs; Crommelin, D.J.A.; de Vlieger, J.S.B., Eds.; Springer International Publishing: Switzerland, 2015, Vol. 20, pp. 171-189.
[3]
Hatahet, T.; Morille, M.; Hommoss, A.; Dorandeu, C.; Muller, R.H.; Begu, S. Dermal quercetin smart crystals: Formulation development, antioxidant activity and cellular safety. Eur. J. Pharm. Biopharm., 2016, 102, 51-63.
[4]
Al Shaal, L.; Shegokar, R.; and Muller, R.H. Production and characterization of antioxidant apigenin nanocrystals as a novel UV skin protective formulation. Int. J. Pharm., 2011, 420(1), 133-140.
[5]
Soliman, G.M. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges. Int. J. Pharm., 2017, 523(1), 15-32.
[6]
Lakshmi, P.; Kumar, G.A. Nanosuspension technology, A review. Int. J. Pharm Sci., 2010, 2(4), 35-40.
[7]
Gupta, M.; Sharma, V.; Chauhan, N.S. Promising novel nanopharmaceuticals for improving topical antifungal drug delivery.In: Nano and Microscale Drug Delivery Systems; Elsevier: Amsterdam, 2017, pp. 197-228.
[8]
Mundstock, A.; Lee, G. Saturation solubility of nicotine, scopolamine and paracetamol in model stratum corneum lipid matrices. Int. J. Pharm., 2014, 473(1-2), 232-238.
[9]
Asghari, F.; Jahanshiri, Z.; Imani, M.; Shams-Ghahfarokhi, M.; Razzaghi-Abyaneh, M. Antifungal nanomaterials: Synthesis, properties, and applications.In: Nanobiomaterials in Antimicrobial Therapy; Elsevier Scienc: Amsterdam, 2016, Vol. 6, pp. 343-383.
[10]
Mishra, P.R.; Al Shaal, L.; Muller, R.H.; Keck, C.M. Production and characterization of Hesperetinnanosuspensions for dermal delivery. Int. J. Pharm., 2009, 371(1), 182-189.
[11]
Mitri, K.; Shegokar, R.; Gohla, S.; Anselmi, C.; Müller, R.H. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int. J. Pharm., 2011, 420(1), 141-146.
[12]
Romero, G.B.; Chen, R.; Keck, C.M.; Muller, R.H. Industrial concentrates of dermal hesperidin smart crystals-production, characterization & long-term stability. Int. J. Pharm., 2015, 482(1), 54-60.
[13]
Pireddu, R.; Caddeo, C.; Valenti, D.; Marongiu, F.; Scano, A.; Ennas, G.; Lai, F.; Fadda, A.M.; Sinico, C. Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability. Colloids Surf. B Biointerfaces, 2016, 143, 64-70.
[14]
Seabra, A.B.; Bernardes, J.S.; Favaro, W.J.; Paula, A.J.; Duran, N. Cellulose nanocrystals as carriers in medicine and their toxicities: A review. Carbohydr. Polymers., 2017, 181, 514-527.
[15]
Gao, L.; Liu, G.; Ma, J.; Wang, X.; Zhou, L.; Li, X. Drug nanocrystals: In vivo performances. J. Control. Release, 2012, 160(3), 418-430.
[16]
Veintemillas-Verdaguer, S.; Marciello, M.; del Puerto Morales, M.; Serna, C.J.; Andres-Verges, M. Magnetic nanocrystals for biomedical applications. Prog. Crystal. Growth Character. Mater., 2014, 60(3-4), 80-86.
[17]
Bahiraei, M.; Heshmatian, S. Application of a novel biological nanofluid in a liquid block heat sink for cooling of an electronic processor: Thermal performance and irreversibility considerations. Energy Convers. Manage., 2017, 149, 155-167.
[18]
Carolan, D. Recent advances in germanium nanocrystals: Synthesis, optical properties and applications. Prog. Mater. Sci., 2017, 90, 128-158.
[19]
Malamatari, M.; Taylor, K.M.; Malamataris, S.; Douroumis, D.; Kachrimanis, K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov. Today, 2018, 23(3), 534-547.
[20]
Mondal, S. Preparation, properties and applications of nanocellulosic materials. Carbohydr. Polymers., 2017, 163, 301-316.
[21]
Bohm, B.H.; Muller, R.H. Lab-scale production unit design for nanosuspensions of sparingly soluble cytotoxic drugs. Pharm. Sci. Technol. Today, 1999, 2(8), 336-339.
[22]
Sattar, A.; Chen, D.; Jiang, L.; Pan, Y.; Tao, Y.; Huang, L.; Liu, Z.; Xie, S.; Yuan, Z. Preparation, characterization and pharmacokinetics of cyadox nanosuspension. Sci. Reports., 2017, 7(2289), 1-8.
[23]
Muller, R.H.; Gohla, S.; Keck, C.M. State of the art of nanocrystals-special features, production, nanotoxicology aspects and intracellular delivery. Eur. J. Pharm. Biopharm., 2011, 78(1), 1-9.
[24]
Salazar, J.; Muller, R.H.; Moschwitzer, J.P. Combinative particle size reduction technologies for the production of drug nanocrystals. J. Pharm., 2014, 2014, 1-14.
[25]
Chang, T.L.; Zhan, H.; Liang, D.; and Liang, J.F. Nanocrystal technology for drug formulation and delivery. Front. Chem. Sci. Eng., 2015, 9(1), 1-14.
[26]
Ali, H.S.; Hanafy, A.F. Glibenclamide nanocrystals in a biodegradable chitosan patch for transdermal delivery: Engineering, formulation, and evaluation. J. Pharm. Sci., 2017, 106(1), 402-410.
[27]
Junghanns, J.U.A.; Müller, R.H. Nanocrystal technology, drug delivery and clinical applications. Int. J. Nanomed, 2008, 3(3), 295.
[28]
Balzus, B.; Colombo, M.; Sahle, F.F.; Zoubari, G.; Staufenbiel, S.; Bodmeier, R. Comparison of different in vitro release methods used to investigate nanocarriers intended for dermal application. Int. J. Pharm., 2016, 513(1), 247-254.
[29]
Srivalli, K.M.; Mishra, B. Drug nanocrystals: A way toward scale-up. Saudi Pharm. J., 2016, 24(4), 386-404.
[30]
Muller, R.H.; Keck, C.M. Challenges and solutions for the delivery of biotech drugs–a review of drug nanocrystal technology and lipid nanoparticles. J. Biotechnol., 2004, 113(1-3), 151-170.
[31]
Peltonen, L.; Hirvonen, J. Drug nanocrystals–versatile option for formulation of poorly soluble materials. Int. J. Pharm., 2018, 537(1-2), 73-83.
[32]
Hou, Y.; Shao, J.; Fu, Q.; Li, J.; Sun, J.; He, Z. Spray-dried nanocrystals for a highly hydrophobic drug: Increased drug loading, enhanced redispersity, and improved oral bioavailability. Int. J. Pharm., 2017, 516(1-2), 372-379.
[33]
Dereymaker, A.; Cinghia, G.; Van den Mooter, G. Eudragit® RL as a stabilizer for supersaturation and a substrate for nanocrystal formation. Eur. J. Pharm. Biopharm., 2017, 114, 250-262.
[34]
Dobrovolskaia, M.A. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy. J. Control. Release, 2015, 220, 571-583.
[35]
Sun, B.; Yeo, Y. Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Curr. Opin. Solid State Mater. Sci., 2012, 16(6), 295-301.
[36]
Bolzinger, M.A.; Briançon, S.; Pelletier, J.; Chevalier, Y. Penetration of drugs through skin, a complex rate-controlling membrane. Curr. Opin. Colloid Interface Sci., 2012, 17(3), 156-165.
[37]
Venus, M.; Waterman, J.; McNab, I. Basic physiology of the skin. Surgery, 2010, 28(10), 469-472.
[38]
Gaboriau, H.P.; Murakami, C.S. Skin anatomy and flap physiology. Otolaryngol. Clin. North Am., 2001, 34(3), 555-569.
[39]
Pyo, S.M.; Hespeler, D.; Keck, C.M.; Muller, R.H. Dermal miconazole nitrate nanocrystals− formulation development, increased antifungal efficacy & skin penetration. Int. J. Pharm., 2017, 531(1), 350-359.
[40]
Vidlarova, L.; Romero, G.B.; Hanus, J.; Stepanek, F.; Muller, R.H. Nanocrystals for dermal penetration enhancement–Effect of concentration and underlying mechanisms using curcumin as model. Eur. J. Pharm. Biopharm., 2016, 104, 216-225.
[41]
Ates, G.; Steinmetz, F.P.; Doktorova, T.Y.; Madden, J.C.; Rogiers, V. Linking existing in vitro dermal absorption data to physicochemical properties: contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability. Regul. Toxicol. Pharmacol., 2016, 76, 74-78.
[42]
Doge, N.; Honzke, S.; Schumacher, F.; Balzus, B.; Colombo, M.; Hadam, S.; Rancan, F.; Blume Peytavi, U.; Schafer Korting, M.; Schindler, A.; Ruhl, E. Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact tape stripped or sodium lauryl sulfate exposed ex vivo human skin assessment by intradermal microdialysis and extraction from the different skin layers. J. Control. Release, 2016, 242, 25-34.
[43]
Abdel-Mottaleb, M.; Lamprecht, A. In vivo skin penetration of macromolecules in irritant contact dermatitis. Int. J. Pharm., 2016, 515(1-2), 384-389.
[44]
Bromberg, L.; Liu, X.; Wang, I.; Smith, S.; Schwicker, K.; Eller, Z.; German, G.K. Control of human skin wettability using the pH of anionic surfactant solution treatments. Colloids Surf. B BiointerfacesI, 2017, 157, 366-372.
[45]
Chantasart, D.; Chootanasoontorn, S.; Suksiriworapong, J.; Li, S.K. Investigation of pH influence on skin permeation behavior of weak acids using nonsteroidal anti-inflammatory drugs. J. Pharm. Sci., 2015, 104(10), 3459-3470.
[46]
Zhai, X.; Lademann, J.; Keck, C.M.; Müller, R.H. Dermal nanocrystals from medium soluble actives–physical stability and stability affecting parameters. Eur. J. Pharm. Biopharm., 2014, 88(1), 85-91.
[47]
Karande, P.; Mitragotri, S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim. Biophys. Acta, 2009, 1788(11), 2362-2373.
[48]
Tsakovska, I.; Pajeva, I.; Al Sharif, M.; Alov, P.; Fioravanzo, E.; Kovarich, S.; Worth, A.P.; Richarz, A.N.; Yang, C.; Mostrag-Szlichtyng, A.; Cronin, M.T. Quantitative structure-skin permeability relationships. Toxicology, 2017, 387, 27-42.
[49]
Colombo, M.; Staufenbiel, S.; Ruhl, E.; Bodmeier, R. In situ determination of the saturation solubility of nanocrystals of poorly soluble drugs for dermal application. Int. J. Pharm., 2017, 521(1), 156-166.
[50]
Alshora, D.H.; Ibrahim, M.A.; Alanazi, F.K. Nanotechnology from particle size reduction to enhancing aqueous solubility. Surface Chem. Nanobiomater., 2016, 6, 163-188.
[51]
Gao, L.; Zhang, D.; Chen, M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J. Nanoparticle. Res., 2008, 10(5), 845-862.
[52]
Junyaprasert, V.B.; Morakul, B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J. Pharm. Sci., 2015, 10(1), 13-23.
[53]
Corrias, F.; Schlich, M.; Sinico, C.; Pireddu, R.; Valenti, D.; Fadda, A.M.; Lai, F. Nile red nanosuspensions as investigative model to study the follicular targeting of drug nanocrystals. Int. J. Pharm., 2017, 524(1), 1-8.
[54]
Osborne, D.W.; Amann, A.H. Topical drug delivery formulations.In: Drugs and the Pharmaceutical Sciences; Marcel Dekker Inc.: New York, 1989, Vol. 42, p. 27.
[55]
Tuomela, A. Nanocrystals for drug delivery applications., Helsinki
University Printing House, 2015, pp. 11. Available from: https://pdfs.semanticscholar.org/b2a2/2c584acb2c980b608d2d415a50f285481b26.pdf (Accessed on: 14th April 2018).
[56]
Pireddu, R.; Sinico, C.; Ennas, G.; Marongiu, F.; Muzzalupo, R.; Lai, F.; Fadda, A.M. Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability. Eur. J. Pharm. Sci., 2015, 77, 208-215.
[57]
Wan, S.; Sun, Y.; Qi, X.; Tan, F. Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. Am. Associat. Pharm. Sci., 2012, 13(1), 159-166.
[58]
Chuasuwan, B.; Binjesoh, V.; Polli, J.E.; Zhang, H.; Amidon, G.L.; Junginger, H.E.; Midha, K.K.; Shah, V.P.; Stavchansky, S.; Dressman, J.B.; Barends, D.M. Biowaiver monographs for immediate release solid oral dosage forms: Diclofenac sodium and diclofenac potassium. J. Pharm. Sci., 2009, 98(4), 1206-1219.
[59]
Sastry, N.V.; Singh, D.K.; Thummar, A.D.; Verma, G.; Hassan, P.A. Effect of hydrocarbon surfactants on dexamethasone solubilization into silicone surfactant micelles in aqueous media and its release from agar films as carriers. J. Mol. Liquids., 2017, 225, 11-19.
[60]
Talekar, S.D.; Dave, R.H. Solubility enhancement of a BCS class II drug using granulated fumed silica as an adsorbent. J. Pharm. Res., 2017, 18(6), 1-15.
[61]
Srinarong, P.; Pham, B.T.; Holen, M.; van der Plas, A.; Schellekens, R.C.; Hinrichs, W.L.; Frijlink, H.W. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration. Drug Develop. Indus. Pharm., 2012, 38(4), 490-500.
[62]
Uchiyama, H.; Tozuka, Y.; Imono, M.; Takeuchi, H. Improvement of dissolution and absorption properties of poorly water soluble drug by preparing spray dried powders with α-glucosyl hesperidin. Int. J. Pharm., 2010, 392(1), 101-106.
[63]
Rai, V.K.; Yadav, N.P.; Sinha, P.; Mishra, N.; Luqman, S.; Dwivedi, H.; Kymonil, K.M.; Saraf, S.A. Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery. Carbohydr. Polymers., 2014, 103, 126-133.
[64]
Cientifica predicts drug nanocrystal market will reach US$81.9
billion by 2021. Available at https://pitchengine.com/pitches/ 69aefcbb-87b2-4fb9-a201-d348c55915ab.
[65]
First, U.S. approval for Elan's NanoCrystal formulation. Available
at https://www.pharmaceuticalonline.com/doc/first-us-approval-for-elans-nanocrystal-formu-0001
(Accessed on: August 30th,
2000).
[66]
Moschwitzer, J.P. Drug nanocrystals in the commercial pharmaceutical development process. Int. J. Pharm., 2013, 453(1), 142-156.
[67]
Weissig, V.; Pettinger, T.K.; Murdock, N. Nanopharmaceuticals (part 1): Products on the market. Int. J. Nanomed, 2014, 9, 4357.
[68]
Peltonen, L.; Hirvonen, J.; Laaksonen, T. Drug nanocrystals and nanosuspensions in medicine.In: Handbook of Nanobiomedical Research; World Scientific: Singapore, 2014, Vol. 1, pp. 169-197.
[69]
Brinzolamide. Available at https://www.drugbank.ca/drugs/ DB01194 (Accessed on: January 28th, 2018).
[70]
Robert Harris. Drug nanocrystal technologies for oral drug delivery,
Am. Pharm. Rev., 2016, Available at http://www.americanpharmaceuticalreview.com/Featured-Articles/331624-Drug-Nanocrystal-Technologies-for-Oral-Drug-Delivery (Accessed on: January 27th 2018).
[71]
Nabilone. Available at https://www.drugbank.ca/drugs/DB00486 (Accessed on: January 28th, 2018).
[72]
Dexmethylphenidate. Available at https://www.drugbank.ca/drugs/ DB06701 (Accessed on: January 28th, 2018).
[73]
Shegokar, R.; and Müller, R.H. Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives. Int. J. Pharm., 2010, 399(1-2), 129-139.
[74]
Methylphenidate. Available at https://www.drugbank.ca/ drugs/DB00422(Accessed on: January 28th, 2018)
Related Books
The Art of Nanomaterials
Advanced Materials and Nano Systems: Theory and Experiment - Part 2
Advanced Materials and Nano Systems: Theory and Experiment (Part-1)
Artificial Intelligence for Smart Cities and Villages: Advanced Technologies, Development, and Challenges
SILVER NANOPARTICLES: Synthesis, Functionalization and Applications
Article Metrics
27
4
1
3