Formulation of Hydrophilic Non-aqueous Gel: Drug Stability in Different Solvents and Rheological Behavior of Gel Matrices

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2007 Oct 3

PMID 17909742

Citations 9

Authors

Keat Theng Chow

Lai Wah Chan

Paul W S Heng

Affiliations

Soon will be listed here.

Abstract

Purpose: This study was aimed at formulating a hydrophilic non-aqueous gel for topical delivery of the model moisture-sensitive drug, minocycline hydrochloride (MH).

Methods: Stability study of MH dissolved in water and various hydrophilic non-aqueous solvents was performed over a period of four months in order to select a suitable non-aqueous solvent for MH gel. To improve MH stability, the effect of different cation additives on MH stability in the selected solvent was investigated. Non-aqueous gel matrices were prepared from three different types of hydrophilic polymers in glycerin-propylene glycol mixture with Mg(2+) cation additive. Oscillatory shear rheometry was performed on the gel matrices using a cone-and-plate rheometer.

Results: MH stability was affected by the type of solvent employed and the duration of storage. Different cation additives affected the extent of MH stabilization through MH-cation complex formation. Rheological properties of the non-aqueous gel matrices were significantly affected by the type and concentration of polymer, and the vehicle ratios in the formulations.

Conclusions: MH stabilization could be achieved using the selected glycerin-propylene glycol mixture containing MgCl(2). Gel matrix formulated using this solvent system and 3%w/w N-vinylacetamide/sodium acrylate copolymer had demonstrated the most favorable rheological properties as a gel for topical application.

Citing Articles

The Preparation and Characterization of ,-Dimethyl Acrylamide-Diallyl Maleate Gel/Hydrogel in a Non-Aqueous Solution.

Bhuyan M, Islam M, Jeong J Gels. 2023; 9(8).

PMID: 37623053 PMC: 10453531. DOI: 10.3390/gels9080598.

The application of electrosprayed minocycline-loaded PLGA microparticles for the treatment of glioblastoma.

Arriaga M, Amieva Jr J, Quintanilla J, Jimenez A, Ledezma J, Lopez S Biotechnol Bioeng. 2023; 120(11):3409-3422.

PMID: 37605630 PMC: 10592149. DOI: 10.1002/bit.28527.

Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications.

Zhang Z, Wang Z, Nong J, Nix C, Ji H, Zhong Y Biofabrication. 2015; 7(1):015006.

PMID: 25599696 PMC: 4314726. DOI: 10.1088/1758-5090/7/1/015006.

Rheological characterization of cataplasm bases composed of cross-linked partially neutralized polyacrylate hydrogel.

Wang J, Zhang H, An D, Yu J, Li W, Shen T AAPS PharmSciTech. 2014; 15(5):1149-54.

PMID: 24865937 PMC: 4179668. DOI: 10.1208/s12249-014-0148-1.

Niosomal gel of lornoxicam for topical delivery: in vitro assessment and pharmacodynamic activity.

Kumbhar D, Wavikar P, Vavia P AAPS PharmSciTech. 2013; 14(3):1072-82.

PMID: 23818079 PMC: 3755149. DOI: 10.1208/s12249-013-9986-5.

References

Islam M, Rodriguez-Hornedo N, Ciotti S, Ackermann C . Rheological characterization of topical carbomer gels neutralized to different pH. Pharm Res. 2004; 21(7):1192-9. DOI: 10.1023/b:pham.0000033006.11619.07. View

Loden M, Andersson A, Anderson C, Bergbrant I, Frodin T, Ohman H . A double-blind study comparing the effect of glycerin and urea on dry, eczematous skin in atopic patients. Acta Derm Venereol. 2002; 82(1):45-7. DOI: 10.1080/000155502753600885. View

Needleman I, Martin G, Smales F . Characterisation of bioadhesives for periodontal and oral mucosal drug delivery. J Clin Periodontol. 1998; 25(1):74-82. DOI: 10.1111/j.1600-051x.1998.tb02366.x. View

Wolf R, Wolf D, Tuzun B, Tuzun Y . Contact dermatitis to cosmetics. Clin Dermatol. 2001; 19(4):502-15. DOI: 10.1016/s0738-081x(01)00184-5. View

Petho G . Equilibrium studies on tetracycline-metal ion systems. J Pharm Biomed Anal. 1996; 14(8-10):1025-9. DOI: 10.1016/s0731-7085(96)01734-7. View

Hussar D, NIEBERGALL P, Sugita E, DOLUISIO J . Aspects of the epimerization of certain tetracycline derivatives. J Pharm Pharmacol. 1968; 20(7):539-46. DOI: 10.1111/j.2042-7158.1968.tb09802.x. View

Goulden V, Glass D, Cunliffe W . Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol. 1996; 134(4):693-5. DOI: 10.1111/j.1365-2133.1996.tb06972.x. View

Wu Y, Fassihi R . Stability of metronidazole, tetracycline HCl and famotidine alone and in combination. Int J Pharm. 2005; 290(1-2):1-13. DOI: 10.1016/j.ijpharm.2004.10.015. View

Heng P, Chan L, Chow K . Development of novel nonaqueous ethylcellulose gel matrices: rheological and mechanical characterization. Pharm Res. 2005; 22(4):676-84. DOI: 10.1007/s11095-005-2484-z. View

10.

Hao J, Chan L, Shen Z, Heng P . Complexation between PVP and Gantrez polymer and its effect on release and bioadhesive properties of the composite PVP/Gantrez films. Pharm Dev Technol. 2004; 9(4):379-86. DOI: 10.1081/pdt-200033004. View

11.

Catanzaro J, SMITH Jr J . Propylene glycol dermatitis. J Am Acad Dermatol. 1991; 24(1):90-5. DOI: 10.1016/0190-9622(91)70018-w. View

12.

Duarte H, Carvalho S, Paniago E, Simas A . Importance of tautomers in the chemical behavior of tetracyclinesdagger. J Pharm Sci. 1999; 88(1):111-20. DOI: 10.1021/js980181r. View

13.

Nelis H, De Leenheer A . Metabolism of minocycline in humans. Drug Metab Dispos. 1982; 10(2):142-6. View

14.

Bamba F, Wepierre J . Role of the appendageal pathway in the percutaneous absorption of pyridostigmine bromide in various vehicles. Eur J Drug Metab Pharmacokinet. 1993; 18(4):339-48. DOI: 10.1007/BF03190183. View

15.

Jones D, Woolfson A, Djokic J, Coulter W . Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res. 1996; 13(11):1734-8. DOI: 10.1023/a:1016413428473. View

16.

Yoshioka S, Aso Y, Terao T . Effect of water mobility on drug hydrolysis rates in gelatin gels. Pharm Res. 1992; 9(5):607-12. DOI: 10.1023/a:1015837723851. View

17.

REMMERS E, SIEGER G, DOERSCHUK A . SOME OBSERVATIONS ON THE KINETICS OF THE C.4 EPIMERIZATION OF TETRACYCLINE. J Pharm Sci. 1963; 52:752-6. DOI: 10.1002/jps.2600520809. View

18.

Johnson Jr W . Final report on the safety assessment of PEG-25 propylene glycol stearate, PEG-75 propylene glycol stearate, PEG-120 propylene glycol stearate, PEG-10 propylene glycol, PEG-8 propylene glycol cocoate, and PEG-55 propylene glycol oleate. Int J Toxicol. 2002; 20 Suppl 4:13-26. DOI: 10.1080/10915810152902556. View

19.

Cordoba-Diaz M, Cordoba-Diaz D . A stability study of tetracycline and tetracycline cyclodextrins in tablets using a new HPLC method. J Pharm Biomed Anal. 2001; 26(3):417-26. DOI: 10.1016/s0731-7085(01)00416-2. View

20.

Chang J, Oh Y, Choi H, Kim Y, Kim C . Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm. 2002; 241(1):155-63. DOI: 10.1016/s0378-5173(02)00232-6. View