Login Register Cart 0
Generic placeholder image

Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Development of Pramipexole Hydrochloride Nanocrystals and their Characterization based on In vitro Dissolution Studies

Author(s): Riyaz Momin, Harshita Gupta, Rutu Panchal and Priti J. Mehta*

Volume 10, Issue 4, 2020

Page: [391 - 404] Pages: 14

DOI: 10.2174/2468187310999201023151231

Price: $65

Abstract

Background: There are numerous unavoidable hurdles encountered by scientists to achieve an ideal drug delivery. Among them, the high-water solubility of a therapeutic molecule has been observed as a chief pausing factor that diminishes the biological stay and shortens the half-life of a drug. The ramification of this occurs that patients have to take medications multiple times in a single day to maintain the drug-plasma concentration. These consequences lead to poor pharmacological responses and ultimately do not add any significant outcomes in the betterment of patient’s health. A similar phenomenon has been observed with the delivery of some potent Anti-Parkinson’s medications, for instance, Pramipexole. The current research is aimed at developing the biological residue of Pramipexole Hydrochloride (PRP) based on the counter ion technology that has provided a sojourn release of PRP by retarding the aqueous solubility, which is further characterized using the dissolution study.

Materials & Methods: Initially, the molar ratio of PRP and the selected counter ion, i.e., Disodium Pamoate (NaPAM), was quantified to produce the stable salt. Thereafter, the salt formation was preceded by the precipitation method and this primarily obtained salt is called microcrystals. In the next stage, the microcrystals were characterized by numerous analytical tools such as Differential Scanning Calorimetry (DSC), melting point, and Mass Spectrometry (MS). On the other hand, Ultraviolet Spectroscopy (UV) was used for the simultaneous determination of PRP and NaPAM in the formed salt. After this, the development of nanocrystals from microcrystals was carried out using high-shear homogenization (HSH) with the aid of α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS), employed as a stabilizer. The preceding step was performed by analyzing the particle size. Following this, an in vitro dissolution study was planned using a dialysis bag system (at 6.8 pH buffer) along with vehicle development and characterization being taken into consideration.

Results: An equimolar ratio (1:1) of PRP and counter ion stipulated the complete reaction occurred among them and then considering this ratio (based on the percent loading efficiency (%LE) and complexation efficiency) (%CE), salt preparation was done. Upon analysis of the developed salt (microcrystal), satisfactory outcomes have assured the complete and compatible salt formation. Besides it, simultaneous estimation certified that the presence of PRP and NaPAM in the formulation does not affect each other, qualitatively and quantitatively. Apart from that, the particle size of these nanocrystals was also found in the acceptable range. Furthermore, Pramipexole Pamoate Nanocrystals Salt (PPNS) was formulated, and in vitro dissolution study showed that PPNS was significantly able to extend the release (93.87 % release, i.e., sustainable) up to 48 hours as compared to the standard PRP. Additionally, the developed vehicle was found suitable and stable, both at room temperature and stress conditions.

Conclusion: To sum up, the data gathered here expressed promising results and rendered an insight that PPNS might be a good option (if clinically proven safe and efficacious) in the nearest future to enhance patient compliance by minimizing the daily demand of PRP for Parkinson's patients. According to our knowledge, we are the first ones reporting depot formulation employing nanoconcepts for the cure of Parkinson’s. However, in vivo animal model studies along with pharmacokinetic data, must be designed to establish the safety and efficiency of PPNS.

Keywords: Counterion, disodium pamoate, in vitro dissolution study, long-acting injectable, nanocrystals, parkinson’s disease, pramipexole hydrochloride, precipitation method.

« Previous Next »
Graphical Abstract

[1]
Youdim MBH, Riederer PF. A review of the mechanisms and role of monoamine oxidase inhibitors in Parkinson’s disease. Neurology 2004; 63(7)(Suppl. 2): S32-5.
[http://dx.doi.org/10.1212/WNL.63.7_suppl_2.S32 ] [PMID: 15477584]
[2]
Qian H, Kang X, Hu J, et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 2020; 582(7813): 550-6.
[http://dx.doi.org/10.1038/s41586-020-2388-4 ] [PMID: 32581380]
[3]
Burn D. Parkinson’s disease: treatment. Pharm J 2019; 264: 476-9.
[4]
Simonet C, Tolosa E, Camara A, Valldeoriola F. Emergencies and critical issues in Parkinson’s disease. Pract Neurol 2020; 20(1): 15-25.
[PMID: 31427383]
[5]
Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017; 3(1): 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13 ] [PMID: 28332488]
[6]
Md S, Haque S, Sahni JK, Baboota S, Ali J. New non-oral drug delivery systems for Parkinson’s disease treatment. Expert Opin Drug Deliv 2012; 359-74.
[7]
Remenar JF. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics. Mol Pharm 2014; 11(6): 1739-49.
[http://dx.doi.org/10.1021/mp500070m ] [PMID: 24679167]
[8]
Mittal S, Kirchmeier MJ, Cunningham JJ. Formulation of depot delivery systems Pharmaceutical Dosage Forms-Parenteral Medications. 3rd ed. CRC Press 2016; pp. 171-206.
[9]
Chaudhary K, Patel MM, Mehta PJ. Long-acting injectables: Current perspectives and future promise critical reviews. Crit Rev Ther Drug Carrier Syst 2019; 36(2): 137-81.
[10]
Kalyani M, Surendra P, Sirisha V. Parenteral controlled drug delivery system. Int J Res Pharm Nano Sci 2013; 2: 572-80.
[11]
Sudhakar M, Kancharla R, Rao VU. A review on sustained release injectable depot drug delivery systems. Int J Adv Pharm Sci 2013; 4: 142-58.
[12]
Patel CA, Keraliya RA. Review: Parentral depot drug delivery system. J Drug Deliv Res 2014; 3: 136-46.
[13]
Muralidhar P, Bhargav E. Controlled release injectable drug delivery: An over view. Asian J Biomater Res 2017; 3(1): 6-15.
[14]
Hoffman AS. The origins and evolution of “controlled” drug delivery systems. J Control Release 2008; 132(3): 153-63.
[http://dx.doi.org/10.1016/j.jconrel.2008.08.012 ] [PMID: 18817820]
[15]
Burgess DJ, Wright JC. An introduction to long acting injections and implants Long acting injections and implants. Springer 2012; pp. 1-9.
[http://dx.doi.org/10.1007/978-1-4614-0554-2_1]
[16]
Shen J, Burgess DJ. Drugs for long acting injections and implants Long acting injections and implants. Springer 2012; pp. 73-91.
[http://dx.doi.org/10.1007/978-1-4614-0554-2_5]
[17]
Shen WW. A history of antipsychotic drug development. Compr Psychiatry 1999; 40(6): 407-14.
[http://dx.doi.org/10.1016/S0010-440X(99)90082-2 ] [PMID: 10579370]
[18]
Comaty JE, Janicak PG. Depot neuroleptics. Psychiatr Ann 1987; 17(7): 491-6.
[http://dx.doi.org/10.3928/0048-5713-19870701-14]
[19]
Gupta H, Panchal R, Acharya N, Mehta PJ. Controlled parenteral formulations : an efficacious and favourable way to deliver the anti-psychotic drugs. Curr Psychol Res Rev 2020; 16: 42-59.
[20]
Dadhaniya TM, Sharma OP, Gohel MC, Mehta PJ. Current approaches for in vitro drug release study of long acting parenteral formulations. Curr Drug Deliv 2015; 12(3): 256-70.
[http://dx.doi.org/10.2174/1567201812666150209143731 ] [PMID: 25666683]
[21]
Muthu MS, Agrawal P, Singh RP. Antipsychotic nanomedicine: a successful platform for clinical use. Nanomedicine (Lond) 2014; 9(14): 2071-4.
[http://dx.doi.org/10.2217/nnm.14.164 ] [PMID: 25405791]
[22]
Junghanns JAH. Nanocrystal technology, drug delivery and clinical applications 2008.; 3(3): 295-309..
[23]
Mittapelly N, Thalla M, Pandey G, et al. Long acting ionically paired embonate based nanocrystals of donepezil for the treatment of alzheimer’s disease: a proof of concept study. Pharm Res 2017; 34(11): 2322-35.
[http://dx.doi.org/10.1007/s11095-017-2240-1 ] [PMID: 28808833]
[24]
Mittapelly N, Rachumallu R, Pandey G, et al. Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection. Eur J Pharm Biopharm 2016; 101: 62-71.
[http://dx.doi.org/10.1016/j.ejpb.2016.01.003 ] [PMID: 26850817]
[25]
S- NDA. (pramipexole dihydrochloride) 0.125 3-34..
[26]
Raj R, Wairkar S, Sridhar V, Gaud R. Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity. Int J Biol Macromol 2018; 109: 27-35.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.056 ] [PMID: 29247729]
[27]
Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym 2008; 73(1): 44-54.
[http://dx.doi.org/10.1016/j.carbpol.2007.11.007]
[28]
Benet LZ. The role of BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) in drug development 2013; 102(1): 34-42..
[29]
Meyer JD, Manning MC. Hydrophobic ion pairing: altering the solubility properties of biomolecules. Pharm Res 1998; 15(2): 188-93.
[http://dx.doi.org/10.1023/A:1011998014474 ] [PMID: 9523302]
[30]
D’Addio SM, Prud’homme RK. Controlling drug nanoparticle formation by rapid precipitation. Adv Drug Deliv Rev 2011; 63(6): 417-26.
[http://dx.doi.org/10.1016/j.addr.2011.04.005 ] [PMID: 21565233]
[31]
Souza SD. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm 2014; p. 304757.
[32]
Shen J, Burgess DJ. In vitro dissolution testing strategies for nanoparticulate drug delivery systems : recent developments and challenges 2013.3(5): 409-15.
[http://dx.doi.org/10.1007/s13346-013-0129-z]
[33]
Lonare AA, Patel SR. Antisolvent crystallization of poorly water soluble drugs. Int J Chem Eng Appl 2013; 4(5): 337.
[http://dx.doi.org/10.7763/IJCEA.2013.V4.321]
[34]
Giriraj P, Sivakkumar T. New simple spectrophotometric method for the simultaneous estimation of paracetamol and flupirtine maleate in pure and pharmaceutical dosage form. Eckhardt CJ, editor International Journal of Spectroscopy. 2014.
[http://dx.doi.org/10.1155/2014/968420]
[35]
Sawant RL, Hadawale SD, Dhikale GK, Bansode CA, Tajane PS. Spectrophotometric methods for simultaneous estimation of rabeprazole sodium and aceclofenac from the combined capsule dosage form. Pharm Methods 2011; 2(3): 193-7.
[http://dx.doi.org/10.4103/2229-4708.90362 ] [PMID: 23781455]
[36]
Biagi E, Capuzzi E, Colmegna F, et al. Long-acting injectable antipsychotics in schizophrenia: literature review and practical perspective, with a focus on aripiprazole once-monthly. Adv Ther 2017; 34(5): 1036-48.
[http://dx.doi.org/10.1007/s12325-017-0507-x ] [PMID: 28382557]
[37]
Motiwala FB, Siscoe KS, El-Mallakh RS. Review of depot aripiprazole for schizophrenia. Patient Prefer Adherence 2013; 7: 1181-7.
[PMID: 24265550]
[38]
Larsen C, Larsen SW, Jensen H, Yaghmur A, Østergaard J. Role of in vitro release models in formulation development and quality control of parenteral depots. Expert Opin Drug Deliv 2009; 6(12): 1283-95.
[http://dx.doi.org/10.1517/17425240903307431 ] [PMID: 19941410]
[39]
Jann MW, Ereshefsky L, Saklad SR. Clinical pharmacokinetics of the depot antipsychotics. Clin Pharmacokinet 1985; 10(4): 315-33.
[http://dx.doi.org/10.2165/00003088-198510040-00003 ] [PMID: 2864156]

Rights & Permissions Print Cite
Article Metrics
29
© 2024 Bentham Science Publishers | Privacy Policy