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Current Dentistry

Editor-in-Chief

ISSN (Print): 2542-579X
ISSN (Online): 2542-5803

Research Article

Development and Characterization of Triple Action-Dental Mold

Author(s): Soma Sengupta, Shounak Sarkhel and Biswajit Mukherjee*

Volume 2, Issue 1, 2020

Page: [60 - 69] Pages: 10

DOI: 10.2174/2542579X02666200309124751

Price: $65

Abstract

Aim: The aim of the present study was the preparation and in vitro evaluation of polymeric molds with amoxicillin trihydrate, lidocaine hydrochloride, and metronidazole for sustained drug release for prolonged local action on an affected tooth (during carries and gum problems).

Background: Periodontal diseases with infection and inflammation cause dental pain. For the treatment of dental problems such as dental pain, analgesics with antibiotics are prescribed at the initial stage.

Objective: The main objective of the present study was to develop polymer-based dental mold containing three drugs (amoxicillin trihydrate, lidocaine hydrochloride, and metronidazole) to provide local drug action on the affected tooth or gingiva for a prolonged period of time.

Methods: Dental molds were prepared with drugs and the optimum combination of polymers (determined by initial screening) such as corn zein, carbopol 934 P, gum acacia powder and poloxamer 407 by mixing together in ethanol (95%) followed by solvent evaporation. The developed dental molds were evaluated using different in vitro physio-chemical methods such as tooth adhesion test, percent swelling, surface pH, scanning electron microscopy, drug content and drug-release study by simultaneous UV spectroscopy.

Results: The mean adhesive strength obtained in our formulation was 46.5 g-wt with a surface pH value of 6.5. The percentage of swelling of the dental molds varied from 43% to 73% in 4 h. Scanning electron microscopy (SEM) showed very small and uniformly distributed drug particles in the matrix. Drug loading was high and reproducible. The cumulative percentage release of lidocaine hydrochloride, amoxicillin trihydrate and metronidazole in vitro was about 93.81%, 59.67%, and 48.7%, respectively, over 24 h.

Conclusion: The developed dental mold containing three drugs may be applied to the affected tooth for prolonged drug action locally and an easy option to relieve from dental pain and infection by local drug action.

Keywords: Dental formulation, amoxicillin trihydrate, lidocaine hydrochloride, metronidazole, simultaneous equation, local action.

Graphical Abstract

[1]
Razak PA, Richard KMJ, Thankachan RP, Hafiz KA, Kumar KN, Sameer KM. Geriatric oral health: a review article. J Int Oral Health 2014; 6(6): 110-6.
[PMID: 25628498]
[2]
Okeson JP, Falace DA. Nonodontogenic toothache. Dent Clin North Am 1997; 41(2): 367-83.
[PMID: 9142490]
[3]
Abbott PV. Medical management of dental and oral pain. Aust Prescr 2007; 30: 77-9.
[http://dx.doi.org/10.18773/austprescr.2007.044]
[4]
Fitzgerald RJ, Keyes PH. Demonstration of the etiologic role of streptococci in experimental caries in the hamster. J Am Dent Assoc 1960; 61: 9-19.
[http://dx.doi.org/10.14219/jada.archive.1960.0138 ] [PMID: 13823312]
[5]
Babaahmady KG, Marsh PD, Challacombe SJ, Newman HN. Variations in the predominant cultivable microflora of dental plaque at defined subsites on approximal tooth surfaces in children. Arch Oral Biol 1997; 42(2): 101-11.
[http://dx.doi.org/10.1016/S0003-9969(96)00116-1 ] [PMID: 9134122]
[6]
Liu F. [The relation between the resistance distribution on crown surface and caries] Zhonghua Kou Qiang Yi Xue Za Zhi 1993; 28(1): 47-9.
[PMID: 8222951]
[7]
Belding PH. Destruction of tooth substance by dental caries. Dent Items Interest 1947; 69(10): 965-8.
[PMID: 20266599]
[8]
Haldi J, Wynn W, Bentley KD, Law ML. Dental caries in the albino rat in relation to the chemical composition of the teeth and of the diet. IV. Variations in the Ca/P ratio of the diet induced by changing the calcium content. J Nutr 1959; 67(4): 645-53.
[http://dx.doi.org/10.1093/jn/67.4.645 ] [PMID: 13642153]
[9]
Daniels TE, Silverman S Jr, Michalski JP, Greenspan JS, Sylvester RA, Talal N. The oral component of Sjögren’s syndrome. Oral Surg Oral Med Oral Pathol 1975; 39(6): 875-85.
[http://dx.doi.org/10.1016/0030-4220(75)90108-5 ] [PMID: 1055974]
[10]
Finn SB, Klapper CE, Voker JF. Intra-oral effects upon experimental hamster cariesAdvances in experimental caries research. Washington, DC: American Association for the Advancement of Sciences 1955; pp. 155-68.
[11]
Frank RM, Herdly J, Philippe E. Acquired dental defects and salivary gland lesions after irradiation for carcinoma. J Am Dent Assoc 1965; 70: 868-83.
[http://dx.doi.org/10.14219/jada.archive.1965.0220 ] [PMID: 14257519]
[12]
Karmiol M, Walsh RF. Dental caries after radiotherapy of the oral regions. J Am Dent Assoc 1975; 91(4): 838-45.
[http://dx.doi.org/10.14219/jada.archive.1975.0493 ] [PMID: 1057626]
[13]
Oh E, Luner PE. Surface free energy of ethylcellulose films and the influence of plasticizers. Int J Pharm 1999; 188(2): 203-19.
[http://dx.doi.org/10.1016/S0378-5173(99)00224-0 ] [PMID: 10518676]
[14]
Bruni G, Amici L, Berbenni V, et al. Drug-excipient compatibility studies. Search of interaction indicators. J Therm Anal Calorim 2002; 68(2): 561-73.
[http://dx.doi.org/10.1023/A:1016052121973]
[15]
Douglass AB, Douglass JM. Common dental emergencies. Am Fam Physician 2003; 67(3): 511-6.
[PMID: 12588073]
[16]
Shah N. Oral and dental diseases: Causes, prevention and treatment strategiesNCMH Background Papers•Burden of Disease in India. New Delhi: Ministry of Health, Government of India 2005; pp. 275-8.
[17]
Christensen KS, Cohen AE, Mermelstein FH, et al. The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model. Anesth Analg 2008; 107(6): 2018-24.
[http://dx.doi.org/10.1213/ane.0b013e318187b952 ] [PMID: 19020153]
[18]
Maslamani M, Sedeqi F. Antibiotic and analgesic prescription patterns among dentists or management of dental pain and infection during endodontic treatment. Med Princ Pract 2018; 27(1): 66-72.
[http://dx.doi.org/10.1159/000486416 ] [PMID: 29262417]
[19]
Cope A, Francis N, Wood F, Mann MK, Chestnutt IG. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database Syst Rev 2014; (6): CD010136
[http://dx.doi.org/10.1002/14651858.CD010136.pub2 ] [PMID: 24967571]
[20]
Dana R, Azarpazhooh A, Laghapour N, Suda KJ, Okunseri C. Role of Dentists in Prescribing Opioid Analgesics and Antibiotics: An Overview. Dent Clin North Am 2018; 62(2): 279-94.
[http://dx.doi.org/10.1016/j.cden.2017.11.007 ] [PMID: 29478458]
[21]
Doshi A, Asawa K, Bhat N, et al. Knowledge and practices of Indian dental students regarding the prescription of antibiotics and analgesics. Clujul Med 2017; 90(4): 431-7.
[PMID: 29151794]
[22]
Agnihotry A, Fedorowicz Z, van Zuuren EJ, Farman AG, Al-Langawi JH. Antibiotic use for irreversible pulpitis. Cochrane Database Syst Rev 2016; 2 CD004969
[PMID: 26886473]
[23]
Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv 2014; 21(2): 75-86.
[http://dx.doi.org/10.3109/10717544.2013.838713 ] [PMID: 24102636]
[24]
Pond SM, Tozer TN. First-pass elimination. Basic concepts and clinical consequences. Clin Pharmacokinet 1984; 9(1): 1-25.
[http://dx.doi.org/10.2165/00003088-198409010-00001 ] [PMID: 6362950]
[25]
Shim HJ, Kim YC, Park KJ, et al. Pharmacokinetics of DA-8159, a new erectogenic, after intravenous and oral administration to rats: hepatic and intestinal first-pass effects. J Pharm Sci 2003; 92(11): 2185-95.
[http://dx.doi.org/10.1002/jps.10482 ] [PMID: 14603504]
[26]
van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin Pharmacokinet 1991; 21(1): 11-26.
[http://dx.doi.org/10.2165/00003088-199121010-00002 ] [PMID: 1717195]
[27]
Foster RH, Goa KL. Paroxetine: a review of its pharmacology and therapeutic potential in the management of panic disorder. CNS Drugs 1997; 8(2): 163-88.
[http://dx.doi.org/10.2165/00023210-199708020-00010 ] [PMID: 23338224]
[28]
Mukherjee B, Roy G, Ghosh S. Development of Denticap, a matrix based sustained release formulation for treatment of toothache, dental infection and other gum problem. Curr Drug Deliv 2009; 6(2): 199-207.
[http://dx.doi.org/10.2174/156720109787846270 ] [PMID: 19450227]
[29]
Gupta A, Garg S, Khar RK. Measurement of bioadhesive buccal tablets: design of an in vitro assembly. Indian Drugs 1993; 30(4): 152-5.
[30]
Ghosh S, Roy G, Mukherjee B. Dental mold: a novel formulation to treat common dental disorders. AAPS PharmSciTech 2009; 10(2): 692-702.
[http://dx.doi.org/10.1208/s12249-009-9255-9 ] [PMID: 19466555]
[31]
Hartley G, Mckenzie C, Greenman J, et al. Tongue Microbiota and Malodour: Effects of Metronidazole Mouthrinse on Tongue Microbiota and Breath Odour. Microb Ecol Health Dis 1999; 11(4): 226-32.
[32]
Schlosser R, Hebbes T. Effect of a dedicated oral care program on periodontal status of medically compromised patients at the Toronto Rehabilitation Institute Dental Clinic. Gen Dent 2016; 64(4): e5-9.
[PMID: 27367641]
[33]
Orosz SE, Jones MP, Cox SK, et al. Pharmacokinetics of amoxicillin plus clavulanic acid in blue-fronted amazon parrots (Amazona aestiva aestiva). J Avian Med Surg 2000; 14(2): 107-12.
[http://dx.doi.org/10.1647/1082- 6742(2000)014[0107:POAPCA]2.0.CO;2]
[34]
Bascones-Martinez A, Fiquero-Ruiz E. Periodontal diseases as bacterial infection. Med Oral Patol Oral Cir Bucal 2004; 9(Suppl:101-7): 92-100..
[35]
Akincibay H, Orsal SO, Sengün D, Tözüm TF. Systemic administration of doxycycline versus metronidazole plus amoxicillin in the treatment of localized aggressive periodontitis: a clinical and microbiologic study. Quintessence Int 2008; 39(2): e33-9.
[PMID: 18567166]
[36]
Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev 2007; 18(2) CD004846
[http://dx.doi.org/10.1002/14651858.CD004846.pub2 ] [PMID: 17443559]
[37]
Stoltenberg JL, Osborn JB, Carlson JF, Hodges JS, Michalowicz BS. A preliminary study of intra-pocket topical versus injected anaesthetic for scaling and root planing. J Clin Periodontol 2007; 34(10): 892-6.
[http://dx.doi.org/10.1111/j.1600-051X.2007.01128.x ] [PMID: 17850608]
[38]
Kasaj A, Heib A, Willershausen B. Effectiveness of a topical salve (Dynexan) on pain sensitivity and early wound healing following nonsurgical periodontal therapy. Eur J Med Res 2007; 12(5): 196-9.
[PMID: 17513190]
[39]
Leopold A, Wilson S, Weaver JS, Moursi AM. Pharmacokinetics of lidocaine delivered from a transmucosal patch in children. Anesth Prog 2002; 49(3): 82-7.
[PMID: 15384296]
[40]
Manasadeepa R, Paul P, Mukherjee B. Pressure-sensitive mucoadhesive polymer-based dental patches to treat periodontal diseases: an in vitro study. Drug Deliv 2013; 20(6): 258-67.
[http://dx.doi.org/10.3109/10717544.2013.823330 ] [PMID: 23869789]
[41]
Mandal D, Shaw TK, Dey G, et al. Preferential hepatic uptake of paclitaxel-loaded poly-(d-l-lactide-co-glycolide) nanoparticles - A possibility for hepatic drug targeting: Pharmacokinetics and biodistribution. Int J Biol Macromol 2018; 112: 818-30.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.02.021 ] [PMID: 29421493]
[42]
Dutta L, Mukherjee B, Chakraborty T, et al. Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood-brain barrier into brain. Drug Deliv 2018; 25(1): 504-16.
[http://dx.doi.org/10.1080/10717544.2018.1435749 ] [PMID: 29426257]
[43]
Mondal L, Mukherjee B, Das K, et al. CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice. Int J Nanomedicine 2019; 14: 8073-94.
[http://dx.doi.org/10.2147/IJN.S220740 ] [PMID: 31632019]
[44]
Dutta D, Paul B, Mukherjee B, et al. Nanoencapsulated betulinic acid analogue distinctively improves colorectal carcinoma in vitro and in vivo. Sci Rep 2019; 9(1): 11506.
[http://dx.doi.org/10.1038/s41598-019-47743-y ] [PMID: 31395908]
[45]
Chakraborty S, Ehsan I, Mukherjee B, et al. Therapeutic potential of andrographolide-loaded nanoparticles on a murine asthma model. Nanomedicine (Lond) 2019. 20102006
[http://dx.doi.org/10.1016/j.nano.2019.04.009 ] [PMID: 31059793]
[46]
Sengupta S, Paul P, Mukherjee B, et al. Peripheral nerve targeting by procaine-conjugated ribavirin-loaded dual drug nanovesicle. Nanomedicine (Lond) 2018; 13(23): 3009-23.
[http://dx.doi.org/10.2217/nnm-2018-0192 ] [PMID: 30507340]
[47]
Bhattacharya S, Mondal L, Mukherjee B, et al. Apigenin loaded nanoparticle delayed development of hepatocellular carcinoma in rats. Nanomedicine (Lond) 2018; 14(6): 1905-17.
[http://dx.doi.org/10.1016/j.nano.2018.05.011 ] [PMID: 29802937]
[48]
Salz U, Bock T. Testing adhesion of direct restoratives to dental hard tissue - a review. J Adhes Dent 2010; 12(5): 343-71.
[PMID: 20978636]
[49]
Semalty A, Bhojwani M. Design and evaluation of mucoadhesive buccal films of diltiazem hydrochloride. Indian J Pharm Sci 2005; 67(5): 548-52.
[50]
Patel VM, Prajapati BG, Patel HV, Patel KM. Mucoadhesive bilayer tablets of propranolol hydrochloride. AAPS PharmSciTech 2007; 8(3) E77
[http://dx.doi.org/10.1208/pt0803077 ] [PMID: 17915827]
[51]
Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing. Int J Pharm 2003; 264(1-2): 1-14.
[http://dx.doi.org/10.1016/S0378-5173(03)00371-5 ] [PMID: 12972331]
[52]
Barat R, Srinatha A, Pandit JK, et al. Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug. Drug Deliv 2006; 13(5): 365-73.
[http://dx.doi.org/10.1080/10717540500398126 ] [PMID: 16877312]
[53]
Dawes C. Salivary flow patterns and the health of hard and soft oral tissues. J Am Dent Assoc 2008; 139(Suppl.): 18S-24S.
[http://dx.doi.org/10.14219/jada.archive.2008.0351 ] [PMID: 18460676]
[54]
Merchant HA, Shoaib HM, Tazeen J, Yousuf RI. Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: A technical note. AAPS PharmSciTech 2006; 7(3): E178-83.
[http://dx.doi.org/10.1208/pt070378 ] [PMID: 28290013]
[55]
Dey NS, Mukherjee B, Maji R, Satapathy BS. Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer. Curr Cancer Drug Targets 2016; 16(4): 357-72.
[http://dx.doi.org/10.2174/1568009616666151106120606 ] [PMID: 26548758]
[56]
Devarajan S, Lakshmi S. Simultaneous spectrophotometric determination of valdecoxib and tizanidine in tablets. Indian J Pharm Sci 2006; 68(2): 240-2.
[http://dx.doi.org/10.4103/0250-474X.25725]
[57]
Giriraj P, Sivakkumar T. New Simple Spectrophotometric Method for the Simultaneous Estimation of Paracetamol and Flupirtine Maleate in Pure and Pharmaceutical Dosage Form. Int J Spectrosc 2014. 968420
[http://dx.doi.org/10.1155/2014/968420]
[58]
Attia KAM, El-Abasawi NM, El-Olemy A, Abdelazim AH. Application of different spectrophotometric methods for simultaneous determination of elbasvir and grazoprevir in pharmaceutical preparation. Spectrochim Acta A Mol Biomol Spectrosc 2018; 189: 154-60.
[http://dx.doi.org/10.1016/j.saa.2017.08.026 ] [PMID: 28806701]
[59]
Shetty PR, Patil DD. Applications of simultaneous equation method and derivative method for the determination of rabeprazole sodium and levosulpiride in pharmaceutical dosage form and dissolution samples. J Assoc Arab Uni Basic App Sci 2014; 15: 53-60.
[http://dx.doi.org/10.1016/j.jaubas.2013.05.005]
[60]
Dange YD, Salunkhe VR, Bhinge S, et al. Simultaneous equation method for the estimation of palbociclib and letrozole by uv-visible spectrophotometry. Indian Drugs 2017; 54(9): 61-6.
[61]
Sharma R, Pathodiya G, Mishra GP, et al. Spectrophotometric Methods for Simultaneous Estimation of Paracetamol and Diclofenac Sodium in Combined Dosage Form by Application of Hydrotropic Solubilization. J Pharm Sci & Res 2010; 2(12): 821-6.
[62]
Rao KS, Banerjee A, Keshar NK. Spectrophotometric methods for the simultaneous estimation of ofloxacin and tinidazole in bulk and pharmaceutical dosage form. Chron Young Sci 2011; 2(2): 98-102.
[http://dx.doi.org/10.4103/2229-5186.82974]
[63]
Brittain HG. Solid-state fluorescence of the trihydrate phases of ampicillin and amoxicillin. AAPS PharmSciTech 2005; 6(3): E444-8.
[http://dx.doi.org/10.1208/pt060355 ] [PMID: 16354003]
[64]
Abu-Huwaij R, Assaf S, Salem M, Sallam A. Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization. Drug Dev Ind Pharm 2007; 33(8): 855-64.
[http://dx.doi.org/10.1080/03639040701377516 ] [PMID: 17729103]
[65]
Singh SK, Fan LT. A generalized model for swelling-controlled release systems. Biotechnol Prog 1986; 2(3): 145-56.
[http://dx.doi.org/10.1002/btpr.5420020309 ] [PMID: 20568207]
[66]
Collys KD, Roma de Sousa AC, Smeyers-Verbeke J. Soluble denture adhesives: pH and sodium content. Eur J Prosthodont Restor Dent 1997; 5(2): 63-7.
[PMID: 9487813]
[67]
Singh B, Ahuja N. Development of controlled-release buccoadhesive hydrophilic matrices of diltiazem hydrochloride: optimization of bioadhesion, dissolution, and diffusion parameters. Drug Dev Ind Pharm 2002; 28(4): 431-42.
[http://dx.doi.org/10.1081/DDC-120003004 ] [PMID: 12056536]
[68]
Badran D, Soutar DS, Robertson AG, et al. Scanning electron microscopy of the surface morphology of superficial cells of buccal mucosa is unlikely to be useful in monitoring radiotherapy. Clin Anat 1994; 7(1): 34-41.
[http://dx.doi.org/10.1002/ca.980070107]
[69]
Hamada S, Torii M, Kotani S, Tsuchitani Y. Adherence of Streptococcus sanguis clinical isolates to smooth surfaces and interactions of the isolates with Streptococcus mutans glucosyltransferase. Infect Immun 1981; 32(1): 364-72.
[http://dx.doi.org/10.1128/IAI.32.1.364-372.1981 ] [PMID: 6452415]
[70]
Mukherjee B, Das S, Patra B, et al. Nefopam containing transdermal- matrix based on pressure-sensitive adhesive polymers. Pharmaceutical Technology (USA) 2006; 30: 146-63.
[71]
Kakish HF, Tashtoush B, Ibrahim HG, Najib NM. A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium. Eur J Pharm Biopharm 2002; 54(1): 75-81.
[http://dx.doi.org/10.1016/S0939-6411(02)00035-8 ] [PMID: 12084505]
[72]
McCauley JA, Brittain HG. Thermal methods of analysisPhysical characterization of pharmaceutical solids. New York: Marcel Dekker 1995; pp. 223-52.
[http://dx.doi.org/10.1201/b14204-9]
[73]
Kötting C, Gerwert K. Monitoring protein-ligand interactions by time-resolved FTIR difference spectroscopy. Methods Mol Biol 2013; 1008: 299-323.
[http://dx.doi.org/10.1007/978-1-62703-398-5_11 ] [PMID: 23729257]
[74]
Wong SM, Kellaway IW, Murdan S. Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles. Int J Pharm 2006; 317(1): 61-8.
[http://dx.doi.org/10.1016/j.ijpharm.2006.03.001 ] [PMID: 16647232]
[75]
Bussemer T, Bodmeier R. Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles. Int J Pharm 2003; 267(1-2): 59-68.
[http://dx.doi.org/10.1016/j.ijpharm.2003.07.008 ] [PMID: 14602384]
[76]
Gulsen D, Chauhan A. Effect of water content on transparency, swelling, lidocaine diffusion in p-HEMA gels. J Membr Sci 2006; 269(1-2): 35-48.
[http://dx.doi.org/10.1016/j.memsci.2005.06.024]
[77]
Song M, Li N, Sun S, Tiedt LR, Liebenberg W, de Villiers MM. Effect of viscosity and concentration of wall former, emulsifier and pore-inducer on the properties of amoxicillin microcapsules prepared by emulsion solvent evaporation. Farmaco 2005; 60(3): 261-7.
[http://dx.doi.org/10.1016/j.farmac.2004.11.009 ] [PMID: 15784247]
[78]
Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 2010; 1: 149-73.
[http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847 ] [PMID: 22432577]
[79]
Pino CJ, Scherer MA, Shastri VP. Investigation of the transdermal transport of charged local anesthetics in the presence of triterpene saponin glycosides. Drug Deliv Transl Res 2014; 4(2): 131-8.
[http://dx.doi.org/10.1007/s13346-013-0186-3 ] [PMID: 25786727]
[80]
Dong W, Bodmeier R. Encapsulation of lipophilic drugs within enteric microparticles by a novel coacervation method. Int J Pharm 2006; 326(1-2): 128-38.
[http://dx.doi.org/10.1016/j.ijpharm.2006.07.013 ] [PMID: 16942845]

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