EXTENDED-RELEASE PROROXANE TABLETS: DESIGN OF COMPOSITION AND INVESTIGATION OF DRUG RELEASE

Download full text PDF
DOI: https://doi.org/None
Issue: 
8
Year: 
2016

G.O. Nifontova (1,2); S.P. Krechetov (1), MD; O.V. Dolotova (1), PhD; E.V. Korostylev (3); A.R. Akhmetzyanova (4); Professor I.I. Krasnyuk (2), PhD 1 -Center of Living Systems, Moscow Institute of Physics and Technology; 9, Institutsky Lane, Build. 7, Dolgoprudnyi, Moscow Region 141700, Russian Federation 2 -I.M. Sechenov First Moscow State Medical University; 8, Trubetskaya St., Build. 2, Moscow 119991, Russian Federation 3 -Сenter for Collective Use, Moscow Institute of Physics and Technology; 9, Institutsky Lane, Dolgoprudnyi, Moscow Region 141700, Russian Federation 4 -Farmzashchita (Pharmprotection) Research-and-Production Center, Federal Bio-medical Agency of Russia; 11, Vashutinskoe Shosse, Khimki, Moscow Region 141402, Russian Federation

Introduction. The short-term effect and high dosages of the oral non-selective α-adrenoceptor proroxane indicate that it is appropriate to design the drug as ex-tended-release tablets that can be retained in the stomach. Objective: to provide evidence for the composition and technology of extended-release proroxane tablets based on hydrophilic matrices. Material and methods. The solubility of proroxane was investigated by the shake-flask method to determine its amount in the samples using high performance liquid chromatography. The size and morphology of proroxane powder particles were ex-amined using optical and electron microscopy. Hydrophilic hydroxypropyl methyl-cellulose (HPMC) matrix tablets were prepared by direct compression. The disso-lution test results were used to evaluate proroxane release from the tablets. Results. The use of hydrophilic HPMC matrix allows for providing the required indicators of the extended release of proroxane from the tablets. The specific fea-tures of the substance of proroxane do not enable one to obtain tableting mixtures with the optimum flowability and they require pregranulation of the substance. Conclusion. The release prolongation focused on the maximum release of prorox-ane hydrochloride in the stomach provides HPMC matrix and the filler microcrys-talline cellulose. When choosing a method of granulation, one should take into ac-count the specific features of both the substance and excipients.
Keywords: 
proroxane
solubility
pH
extended release
hydrophilic matrices
References: 
  1. Vinichuk S.M., Turchina N.S., Vinichuk I.S. Primenenie α-adrenoblokatora pirroksana pri lechenii vegetativnyh krizov u bol`nyh s myagkoy formoy arterial`noy gipertenzii. Semeynaya medicina, 2005; 2: 86–9. [Vinichuk S.M., Turchina N.S., Vinichuk I.S. Alpha-adrenoblocker proroxan treatment of mild hypertension patients’ vegetative crises. Semejnaja medicina, 2005; 2: 86–9 (in Russian)].
  2. Vorob`ev S.P., Gromov S.A., Staryh N.T. Lechenie pirroksanom bol`nyh die`ncefal`noy e`pilepsiey. Zhurnal nevropatologii i psihiatrii, 1973;11: 1732–5. [Vorob'ev S.P., Gromov S.A., Staryh N.T. Pyrroxan therapy of patients with diencephalic epilepsy. Zh. Nevropatol. Psikhiatr. Im. S. S. Korsakova., 1973; 11:1732–1735. (in Russian)].
  3. Burykina G.N. Novyy otechestvennyy preparat pirroksan v terapii bol`nyh allergicheskimi dermatozami. Vestnik dermatologii i venerologii, 1974; 12: 63–6. [Burykina G.N. New Soviet preparation of pyrroxan in the treatment of patients with allergic dermatoses. Vestn.Dermatol.Venerol., 1974; 12: 63–6 (in Russian)].
  4. Krylova S.A., Krylov S.S., Petrov A.N. Raspredelenie adrenoblokiruyushhego preparata pirroksana v organizme belyh krys. Byulleten` e`ksperimental`noy biologicheskoy mediciny, 1976; 12: 1453–5. [Krylova S.A., Krylov S.S., Petrov A.N. Distribution of the adrenoblocking drug pyrroxan in the bodies of white rats. Biull. Eksp. Biol. Med., 1976; 12: 1453–5 (in Russian)].
  5. Maderuelo C., Zarzuelo A., Lanao J.M. Critical factors in the release of drugs from sustained release hydrophilic matrices. J. Control. Release. 2011 Aug. 25; 154 (1): 2–19.
  6. Alekseev K.V., Blynskaya E.V., Karbusheva E.Yu., Sedova M.K., Tihonova N.V., Uvarov N.A. Poluchenie plavayushhih lekarstvennyh form. Farmaciya, 2012; 6: 35–8. [Alekseev K.V., Blynskaja E.V., Karbusheva E.Ju., Sedova M.K., Tihonova N.V., Uvarov N.A. Preparation of floating dosage forms. Farmatsiya, 2012; 6: 35–38. (in Russian)].
  7. Timmins P., Pygall S.R., Melia C.D. Hydrophilic Matrix Tablets for Oral Controlled Release, New York: Springer; 2014; 326.