Review Articles

2018  |  Vol: 3(2)  |  Issue: 2(March-April) | https://doi.org/10.31024/apj.2018.3.2.1
Applications of natural polymers in mucoadhesive drug delivery: An overview

Ashish Garg1, Sweta Garg1, Manish Kumar2, Suresh Kumar2, Ajay Kumar Shukla2*, Satya Prakash Chand Kaushik3

1Department of P.G. Studies and Research in Chemistry and Pharmacy, Rani Durgavati University, Jabalpur, India.

2Department of Pharmaceutical Science, Mohan Lal Sukhadiya University, Rajasthan, India

3Dept. of Pharmaceutics, Jaipur College of Pharmacy, Jaipur, Rajasthan, India.

*Address for Corresponding Author:

Ajay Kumar Shukla

Department of Pharmaceutical Sciences,

Mohanlal Sukhadia University Udaipur 313001 Rajasthan India


Abstract

Aim of this review is to compile the current literature with special focus on role of natural polymers on mucoadhesive drug delivery system. Mucodhesion refers to bond formed between two biological surfaces or a bond connecting a biological and a synthetic polymer surface. Under this drug delivery, buccal mucosa is the preferred site for both systemic and local drug action because the mucosa has a rich blood supply and it relatively permeable. Different bioadhesive dosages form available in market such as Chewing gum, tablets, Patches, Hydrogel, Thiolated tablets. In this review article the Application of natural mucoadhesive polymers advantages, disadvantages and future prospects in Buccal drug delivery has been discussed.

Keywords: Anatomy of oral mucosa, buccal, mucoadhesive polymer, permeation, dissolution


Introduction

The general availability of drugs taken orally may be limited by the g.i.t transit time of the drug delivery system. This is particularly so far drugs those are majorly absorbed from the intestine. There availability is limited by the residence time of the drugs in or upstream of the small intestine. This type of drug easlity to deliver through mucoadhesive drug delivery systems. In mucoadhesive drug delivery systems basically the drugs are incorporated in a polymer that has the mucoadhesive properties (Chowdary et al., 2000).

Definition of bio adhesion

In bio adhesive drug delivery systems, the term bio adhesion is used to describe the bonding or adhesion between synthetic or natural polymer soft tissues like as epithelial cells. The term mucoadhesion is used to describe adhesion interactions between polymers and mucus or mucosal surfaces (Nagai et al., 1987).

Advantages

Mucoadhesive dosage forms facilitate increase contact of the formulation with the underlying absorption surface of the body consequently macromolecules such as peptides and proteins are easiliy to absorb in the body. In mucoadhesive formulation developed with penetration enhancers’ agents such as sodium glycocholate, sodium tauochaolate, L-Lysophos photidyl choline 9LPLO and protease inhibitors in resulted better absorption of peptides macromolecules into the body. It prolongs the residence time of the dosage form at the site of application, absorption and increase the action of drug (Duchene et al., 1988).

Buccal Drug Delivery and Mucoadhesivity

In buccal drug delivery systems, mucoadhesion property of formulation is the key element. For proper and good mucoadhesion property depends on nature of polymer. The mucoadhesive polymers currently used for the development of different dosages form such as tablets, patches, tapes, films, semisolids and powders. Many studies reported that due to utilization of various mucoadhesive polymers to drug delivery systems, increased the duration of attachment and efficacy of the drug. The mucoadhesive polymers should possess some general physiochemical features such as predominantly anionic hydrophilicity with numerous hydrogen bond-forming groups. Natural polymer and its degradation products should be non-toxic, non-irritant and free from leachable impurities.

Natural polymers

The polymers within this category are soluble in water. Matrices developed with these polymers swell when they come in contact an aqueous media with subsequent dissolution of the matrix. The polyelectrolytes widen greater mucoadhesive property such as. poloxamer, hydroxypropyl methyl cellulose, methyl cellulose, poly (vinyl alcohol) and poly (vinyl pyrrolidone), have been used for mucoadhesive properties. The natural polysaccharides and its derivatives like chitosan, methyl cellulose, hyaluronic acid, hydroxy propyl methylcellulose, hydroxy propyl cellulose, Xanthan gum, gellan gum, guar gum, and Carrageenan have been utilized in development of ocular drug delivery systems. Cellulose and its derivates have been reported to have surface active property in addition to its film forming capability. Cellulose derivatives with lower surface acting property are normally preferred in ocular delivery systems as they cause reduced eye irritation. Cationic cellulose derivatives (e.g. cationic hydroxyethyl celluloses) have been used in conjunction with various anionic polymers for the development of sustained delivery systems (Shukla et al., 2017; Shukla et al., 2018).

Characteristics of an ideal Mucoadhesive Polymer

An ideal mucoadhesive polymer has the following characteristic

1. They must be nontoxic and should be non-absorbable from the gastrointestinal tract.

2. It must be nonirritant to the mucous membrane.

3. It must preferably form a strong non-covalent bond with the mucin-epithelial cell surfaces.

4. It must adhere quickly to most tissue and should possess some site-specificity.

5. It must allow daily incorporation to the drug and offer no hindrance to its release.

6. The polymer should not decompose on storage or during the shelf life of the dosage form.

7. The cost of polymer should not be very high so that the prepared dosage form remains competitive (Girish et al., 2009).

Disadvantages of Natural polymers (Shirwaikar et al., 2008)

1. They are easily to microbial degradation.

2. Batch to batch variation come.

3. The unreserved rate of hydration.

4. Heavy metal adalteration.

Table 1. List of polymers used in formulation of various drug delivery systems.

Name of polymer

Formulation

Reference

Karya gum

Developed and evaluated gastric retentive gel for rodents in situ, using a mixture of sodium alginate and karaya gum. Feasibility studies were conducted in Sprague-Dawley rats using barium sulfate as a radio-opaque tracer.

Developed modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug, nimodipine.

Foster et al., 2012 ;Murali Mohan Babu et al., 2002

Xanthan gum

Sustained-release and swelling characteristics of xanthan gum/ethylcellulose-based injection moulded matrix tablets: in vitro and in vivo evaluation.

Statistical evaluation of influence of xanthan gum and guar gum blends on dipyridamole release from floating matrix tablets.

Xanthan and its binary blends with synthetic polymers to design controlled release formulations of buccoadhesive nystatin tablets.

Quinten et al., 2011 ;Patel et al., 2007 ; Sakeer et al., 2010

Guar gum

Guar gum-based sustained release diltiazem

evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug

Altaf et al., 1998; Al-Saidan et al., 2004

Tragacanth

Common Natural Ingredients Used in Food, Drugs and Cosmetics

Leung  et al., 1980

Pectin

on the gelling behaviour of ‘nopal’ (Opuntia ficus indica) low metholoxyl pectin

Cárdenas et al., 2008

Chitosan

Propranolol hydrochloride, buccal film

Metoprolol tartarate, buccal patches

Cetylpyridinium chloride, buccal patches

Curcumin, buccal patches

Propranolol hydrochloride, buccal patches

Resperidone, buccal patches

Salbutamol sulphate, buccal patches

Verapamil HCL , buccal patches

buccal patches of Lornoxica

Angela et al., 2011; Furtado et al., 2010; Nafee et al., 2003; Das et al., 2001; Patel et al., 2007; Manasa et al., 2010; Patel et al., 2009; Deshmane et al., 2009; Kumar et al., 2010

Gum Arabic

Natural gums and modified natural gums as sustained-release carriers

Encapsulation of endoglucanase using a biopolymer gum arabic for its controlled release

Bhardwaj et al., 2000; Ramakrishnan et al., 2007

Locust bean gum

Carboxymethyl ethers of locust bean gum

Physicochemical Characterization and Dissolution Study of Ibuprofen Compression-Coated Tablets Using Locust Bean Gum

Dey et al., 2011; Bashardoust et al., 2013

Grewia gum

Effect of grewia gum as a suspending agent on ibuprofen pediatric formulation

Ogaji et al., 2011

Bhara Gum

Design and Evaluation of controlled release bhara gum microcapsules of famotidin e for oral use

Nayak et al., 2008

Mango Gum

Evaluation of disintegrating properties of Mangifera indica

Kumar et al., 2011

Gelatin

Sumatriptan succinate, Mucoadhesive bilayered patches

Aceclofenac of Mucoadhesive buccal patch  

Shidhaye et al., 2008; Khairnar et al., 2009

Fenugreek gum

The Potential of Trigonella foenumgraecum

L. Seed Mucilage as Suspending Agent

Nayak et al., 2012

Tamarind gum

Various studies have been conducted on the buccal delivery of drugs using mucoadhesive polymers primarily polysaccharides

Bottari et al., 1975

Table 2. Marketed oral mucoadhesive drug delivery systems

Drugs

Dosage form

Type of release

Products name

Manufacturer

Chlorhexidine

Hydrocortisone sodium succinate

Oromucosal gel

 

Controlled

 

Corsodyl gel

 

GalaxoSmithKline

 

Hydrocortisone sodium succinate

Oromucosal pallets

Controlled

Corlan pellets

Celltech

Buprenorphine HCl and Naloxone

Tablet

Quick

Sulbutex

Reckitt Benckiser

Proclorperazine

Tablet

Controlled

Buccastem

Reckitt Benckiser

Testosterone

Tablet

Controlled

Straint SR

Columbia

Zolpidem

Spray

Quick

Zolpimist

Pharmaceuticals

NovaDel

Future perception

Natural mucoadhesive polymers increase bioadhesion time of drug molecules; this property of formulation can utilized in wide variety of drugs administration for improvement in specific therapies, efficacy and more general patient compliance. Hence mucoadhesive natural polymers can be used as means of improving drug delivery other than different routes like gastrointestinal, nasal, ocular, buccal, vaginal and rectal. Many prospective mucoadhesive systems are being investigate which may find their way into the market in near future. Natural polymers have vast potential for the delivery of therapeutic macromolecules, genes, and vaccines. Unfortunately, only a few studies have been conducted with new generation mucoadhesive natural polymers for novel drug delivery, and very few papers focus on the changes of structure and rheology of the mucus caused by the mucoadhesive polymer, to what extent the interaction between the polymer and the mucus influences the release of the drugs including in the disease condition. The various sites where mucoadhesive natural polymers have played an important role include buccal cavity, soft palate, gingival, nasal cavity, rectal lumen, vaginal lumen and gastrointestinal tract with recent advancements in the fields of biotechnology and cytoadhesion, the authors believe that there will be both academic and industrial efforts to explore this new area of mucoadhesive like  nasal drug delivery, and it might not be too far-fetched to envisage more and more nasal products that employ mucoadhesive polymers.

Conclusion

Mucoadhesive drug delivery system proves to be a only alternative to conventional drugs by popular quality of its ability in overcoming hepatic metabolism, reduction in dose frequencies and enhancing bioavailability. Natural polymers used as mucoadhesive polymers. It facilitates an important tool to improve the bioavailability of the bioactive agent by improving the residence time at the delivery site. Improvement of novel natural mucoadhesive delivery systems are being undertaken so as to understand the various mechanism of mucoadhesion and improved permeation of active agents. Mucoadhesive drug delivery systems required to more work for the development of ideal mucoadhesive polymer which can deliver the drug very easily.

References

Al-Saidan SM, Krishnaiah YS, Satyanarayana V, Bhaskar P, Karthikeyan RS. 2004. Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug. European Journal of Biopharmaceutics, 58(3):697-703.

Altaf SA, Yu K, Parasrampuria J, Friend DR. 1998. Guar gum-based sustained release diltiazem. Pharmaceutical Research, 15(8):1196-1201.

Angela A, Federica B, Teresa C, Federica C, Beatrice V, Barbara L. 2011. Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydrate Polymers 87(1):581-588.

Bashardoust N, LenoJenita JJ, Zakeri–Milani P. 2013. Physicochemical characterization and dissolution study of ibuprofen compression-coated tablets using locust bean gum. Dissolution Technology, 38-43.

Bhardwaj TR, Kanwar M, Lal R., Gupta A. 2000. Natural gums and modified natural gums as sustained-release carriers. Drug Development and Industrial Pharmacy, 26:1025-1038.

Chowdary KPR. 2000. A Review on current status on mucoadhesive drug delivery system. Indian Drugs, 37(9):400.

Das R. 2001. Effective mucoadhesive buccal patches: wound healing activity of curcumin & centella asiatica extract compared to rhEGF. International Journal of Pharmacy and Pharmaceutical Sciences, 3(1):97-100.

Deshmane SV, Channawar MA, Chandewar AV, Joshi UM, Biyani KR.. 2009.  Chitosan based sustained release mucoadhesive buccal patches containing verapamil HCL. International Journal of Pharmacy and Pharmaceutical Sciences, 1(1):216-229.

Dey P, Sa B, Maiti S. 2011. Carboxymethyl ethers of locust bean gum-A review. International Journal of Pharmacy and Pharmaceutical Sciences, 3:4–7.

Duchene D, Touchard F, Pappas NA. 1988. Pharmaceutical and medical aspects of bioadhesive systems for drug administration. Drug Development and Industrial Pharmacy, 14:283-318.

Foster KA, Morgen M, Murri B, Yates I, Fancher RM, Ehrmann J, Gudmundsson OS, Hageman MJ. 2012. Utility of in situ sodium alginate/karaya gum gels to facilitate gastric retention in rodents. International Journa of Pharmaceutics, 434(1-2):406-412.

Furtado S, Bharath S, Basavaraj BV, Abraham S, Deveswaran R, Madhavan V. 2010. Development of chitosan based bioadhesive bilayered patches of metoprolol tartarate, International Journal of Pharmaceutical Science Review and Research, 4(3):198-202.

Khairnar A, Jain P, Baviskar D, Jain D. 2009. Developmement of mucoadhesive buccal patch containing aceclofenac: in vitro evaluations. International Journal of Pharmaceutical Technology and Research, 1(4):978-981.

Kumar DS, Reddy KS, Tiwari AM, Dey S. 2010. Design and evaluation of buccal patches of lornoxica, International Journal of Pharmacy and Biological Science, 1(4):587-596.

Kumar NR, Sachin R, Mirtyunjaya B. 2011. Evaluation of disintegrating properties of Mangifera indica. RGUHS J Pharm Sci, 1(1):11-20.

Leung AY. 1980. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, New York, NY: J, Wiley and Sons,

Manasa B, Gudas GK, Sravanthi N, Madhuri RA, Lavanya Y, Pranitha C. 2010. Formulation and evaluation of mucoadhesive buccal patches of resperidone. Journal of Chemical and Pharmaceutical Research, 2(4): 866-872.

Murali Mohan Babu G, Kumar NR, Sankar KH, Ram BJ, Kumar NK, Murthy KV. 2002. In vivo evaluation of modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug, nimodipine. AAPS Pharm Sci Tech, 3(2):55-63.

Nafee NA, Ahmed N, Ismail BFA, Mortada LM. 2003. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharm, 53:199-212.

Nagai T, Konishi R. 1987. Buccal/gingival drug delivery systems. Journal of Controlled Release, 6:353-60.

Nayak AK, Pal DK, Pradhan JP, Ghorai T. 2012. The potential of trigonella foenumgraecum seed mucilage as suspending agent. Indian Journal of Pharmaceutical Education and Research, 46(4): 312-317

Nayak BS, Nayak UK, Patro KB, Rout PK. 2008. Design and Evaluation of controlled release bhara gum microcapsules of famotidine for oral use. Research Journal of Pharmacy and Technology, 1:433-436.

Ogaji IJ, Hoag SW. 2011. Effect of grewia gum as a suspending agent on ibuprofen pediatric formulation. AAPS Pharm Sci Tech, 12(2):507-513.

Patel RS, Poddar SS. 2009. Development and characterization of mucoadhesive buccal patches of salbutamol sulphate. Current Drug Delivery, 6:140-144.

Patel VF, Patel NM. 2007. Statistical evaluation of influence of xanthan gum and guar gum blends on dipyridamole release from floating matrix tablets. Drug Development and Industrial Pharmacy, 33(3):327-334.

Patel VM, Prajapati BG, Patel MM. 2007. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride, Acta Pharmaceutica, 57:61–72.

Quinten T, DeBeer T, Onofre FO, Mendez-Montealvo G, Wang YJ, Remon JP, Vervaet C. 2011. Sustained-release and swelling characteristics of xanthan gum/ethylcellulose-based injection moulded matrix tablets: in vitro and in vivo evaluation. Journal of Pharmaceutical  Sciences, 100(7):2858-2870.

Sakeer K, Al-Zein H, Hassan I, Martin GP, Nokhodchi A. 2010. Use of xanthan and its binary blends with synthetic polymers to design controlled release formulations of buccoadhesive nystatin tablets. Pharmaceutical Development Tecnology, 15(4):360-368.

Shidhaye SS, Saindane NS, Sutar S, Kadam V. 2008. Mucoadhesive bilayered patches for administration of sumatriptan succinate, Pharmaceutical Science and Technology, 9(3):909- 916.

Shirwaikar A, Prabu SL, Kumar GA. 2008. Herbal excipients in novel drug delivery systems. Indian Journal of Pharmaceutical Sciences, 70:415-22.

Shukla AK, Bishnoi RS, Kumar M, Fenin V, Jain CP. 2018. Applications of tamarind seeds polysaccharide-based copolymers in controlled drug delivery: An overview. Asian Journal of Pharmacy and Pharmacology, 4(1):23-30

Shukla AK, Kumar M, Bishnoi RS, Jain CP. 2017. Review article application of fenugreek seed gum: in novel drug delivery. Asian Journal of Biomaterial Research, 3(6):1-10

Sinha VR, Kumria R. 2001. Polysaccharides in colon-specific drug delivery. International Journal of Pharmaceutics, 224:19-38.

Tyler VE, Brady LR, Robers JE. 1981. Plant Gums and Mucilage. 8th ed, Lea and Febiger, Philadelphia.

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