Semi-solid materials for controlled release drug formulation: current status and future prospects

Abstract

Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semi-solid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.

Key words： semi-solids; polymer; excipient; controlled release; drug delivery

References

1 Langer R, Tirrell D A. Designing materials for biology and medicine. Nature, 2004, 428(6982): 487–492

2 Benson H, Watkinson A. Topical and Transdermal Drug Delivery: Principles and Practice. Hoboken, NJ: John Wiley & Sons, 2012, 1–407

3 Niazi S. Handbook of Pharmaceutical Manufacturing Formulations, Semisolid Products, Volume 4. Florida: CRC Press, 2004

4 Vashist A, Vashist A, Gupta Y K, Ahmad S. Recent advances in hydrogel based drug delivery systems for the human body. Journal of Material Chemistry B, 2013, 2(2): 147–166

5 Varde N K, Pack D W. Microspheres for controlled release drug delivery. Expert Opinion on Biological Therapy, 2004, 4(1): 35–51

6 Bao G, Mitragotri S, Tong S. Multifunctional nanoparticles for drug delivery and molecular imaging. Annual Review of Biomedical Engineering, 2013, 15(1): 253–282

7 Allen T M, Cullis P R. Liposomal drug delivery systems: from concept to clinical applications. Advanced Drug Delivery Reviews, 2013, 65(1): 36–48

8 Edgar K J. Cellulose esters in drug delivery. Cellulose, 2006, 14(1): 49–64

9 Ravenelle F, Rahmouni M. High-Amylose Starch for Controlled Drug Delivery. Polysaccharides for Drug Delivery and Pharmaceutical Applications. ACS Symposium Series 934, American Chemical Society, 2006, Chapter 4, 79–104

10 Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics, 2012, 81(3): 463–469

11 Tønnesen H H, Karlsen J. Alginate in drug delivery systems. Drug Development and Industrial Pharmacy, 2002, 28(6): 621–630

12 Singla A K, Chawla M, Singh A. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Development and Industrial Pharmacy, 2000, 26(9): 913–924

13 da Fonseca Antunes A B, De Geest B G, Vervaet C, Remon J P. Gelucire 44/14 based immediate release formulations for poorly water-soluble drugs. Drug Development and Industrial Pharmacy, 2013, 39(5): 791–798

14 Hashida M, Takakura Y. Pharmacokinetics in design of polymeric drug delivery systems. Journal of Controlled Release, 1994, 31(2): 163–171

15 Karsa D, Stephenson R. Excipients and Delivery Systems for Pharmaceutical Formulations. Cambridge: Royal Society of Chemistry, 1995, 36–189

16 Wasan K. Role of Lipid Excipients in Modifying Oral and Parenteral Drug Delivery. Hoboken, NJ: John Wiley & Sons, 2007, 1–196

17 Tang B, Cheng G, Gu J C, Xu C H. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discovery Today, 2008, 13(13–14): 606–612

18 Liu H, Ilevbare G A, Cherniawski B P, Ritchie E T, Taylor L S, Edgar K J. Synthesis and structure-property evaluation of cellulose ω-carboxyesters for amorphous solid dispersions. Carbohydrate Polymers, 2014, 100: 116–125

19 Cui L, Jia J, Guo Y, Liu Y, Zhu P. Preparation and characterization of IPN hydrogels composed of chitosan and gelatin cross-linked by genipin. Carbohydrate Polymers, 2014, 99(2): 31–38

20 Liechty W B, Kryscio D R, Slaughter B V, Peppas N A. Polymers for drug delivery systems. Annual Review of Chemical and Biomolecular Engineering, 2010, 1(1): 149–173

21 Marchessault R, Ravenelle F, Zhu X. Polysaccharides for Drug Delivery and Pharmaceutical Applications. Washington, DC: American Chemical Society, 2006, 19–339

22 Pouton C W. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. European Journal of Pharmaceutical Sciences, 2006, 29(3–4): 278–287

23 Pouton C W, Porter C J. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Advanced Drug Delivery Reviews, 2008, 60(6): 625–637

24 Ilevbare G A, Liu H, Edgar K J, Taylor L S. Impact of polymers on crystal growth rate of structurally diverse compounds from aqueous solution. Molecular Pharmaceutics, 2013, 10(6): 2381–2393

25 Wilson C, Crowley P. Controlled Release in Oral Drug Delivery. New York: Springer, 2011, 1–412

26 Badwaik H R, Giri T K, Nakhate K T, Kashyap P, Tripathi D K. Xanthan gum and its derivatives as a potential bio-polymeric carrier for drug delivery system. Current Drug Delivery, 2013, 10(5): 587–600

27 Wen H, Park K. Oral Controlled Release Formulation Design and Drug Delivery: Theory to Practice. John Wiley & Sons, 2010, Chapter 5

28 Li Z, Kozlowski B M, Chang E P. Analysis of aldehydes in excipients used in liquid/semi-solid formulations by gas chromatography-negative chemical ionization mass spectrometry. Journal of Chromatography A, 2007, 1160(1–2): 299–305

29 Gursoy R N, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomedicine and Pharmacotherapy, 2004, 58(3): 173–182

30 Patel P V, Patel H K, Mehta T A, Panchal S S. Self micro-emulsifying drug delivery system of tacrolimus: Formulation, in vitro evaluation and stability studies. International Journal of Pharmaceutical Investigation, 2013, 3(2): 95–104

31 Fernandez S, Rodier J, Ritter N, Mahler B, Demarne F, Carrière F, Jannin V. Lipolysis of the semi-solid self-emulsifying excipient gelucire® 44/14 by digestive lipases. Molecular and Cell Biology of Lipids, 2008, 1781(8): 367–375

32 Inactive ingredient search for approved drug products. Inactive ingredients in FDA approved drugs. US Department of Health & Human Services. 21 Sept. 2013

33 Burgess B E. Optimizing drug delivery for modern biologics. BioPharm International, 2012, 25(5): 30–32

34 Koo O M Y, Varia S A. Case studies with new excipients: development, implementation and regulatory approval. Therapeutic Delivery, 2011, 2(7): 949–956

35 Amsden B G. Liquid, injectable, hydrophobic and biodegradable polymers as drug delivery vehicles. Macromolecular Bioscience, 2010, 10(8): 825–835

36 Rigo M V, Allemandi D A, Manzo R H. Swellable drug–polyelectrolyte matrices (SDPM) of alginic acid characterization and delivery properties. International Journal of Pharmaceutics, 2006, 322(1–2): 36–43

37 Wan J. Microfluidic-based synthesis of hydrogel particles for cell microencapsulation and cell based-drug delivery. Polymers, 2012, 4(4): 1084–1108

38 Heller J. Patient-friendly bioerodible drug delivery systems. Journal of Controlled Release, 2009, 133(2): 88–89

39 Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P. Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chemical Society Reviews, 2013, 42(3): 1147–1235

40 Salamat-Miller N, Chittchang M, Johnston T P. The use of mucoadhesive polymers in buccal drug delivery. Advanced Drug Delivery Reviews, 2005, 57(11): 1666–1691