Author(s): P. M. Kale

Email(s): Email ID Not Available

DOI: 10.52711/2231-5713.2024.00029   

Address: P. M. Kale*
Sr. Lecturer, Shree Ambabai Talim Sanstha’s Diploma in Pharmacy College, Miraj.
*Corresponding Author

Published In:   Volume - 14,      Issue - 2,     Year - 2024

In the present study, inclusion complexes of Efavirenz were developed with HPß-cyclodextrin (HPß-CD). The complexes were prepared by kneading method. Inclusion complexes of with HPß-CD in aqueous solution were evaluated for phase solubility. The phase solubility diagram with the complexing agent was classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constant obtained was 820M1¯. The drug was compatible with the polymers used. It was confirmed by fourier-transform infrared spectra. The study indicated the presence of intermolecular hydrogen bonds between and complexing agent, resulting in the formation of amorphous form. Dissolution profiles were markedly increased in inclusion complexes, compared with the drug alone and physical mixture. Moreover, the inclusion complex prepared by kneading method was shown better aqueous solubility and dissolution profile than complex prepared by physical mixture.

Cite this article:
P. M. Kale. Solubility Enhancement of Efavirenz by Microwave Technology. Asian Journal of Pharmacy and Technology. 2024; 14(2):163-2. doi: 10.52711/2231-5713.2024.00029

P. M. Kale. Solubility Enhancement of Efavirenz by Microwave Technology. Asian Journal of Pharmacy and Technology. 2024; 14(2):163-2. doi: 10.52711/2231-5713.2024.00029   Available on:

1.    Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000; 50: 47-60.
2.    Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics a Treatise. 1st ed. New Delhi: Vallabh Prakashan; 1995.
3.    Rajeswari C, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: An updated review. AAPS Pharm Sci Tech 2005 Jan; E1-102.
4.    Rao BP, Suresh S, Narendra C. Recent advances in cyclodextrin complexes: Mechanistic analysis as permeation enhancer. Indian J Pharm Edu Res 2007 Apr-Jun; 41(2): 102-113.
5.    Marcus EB, Thorsteinn L. Cyclodextrins as pharmaceutical Solubilizers.Advance drug delivery reviews; 59 (2007) 645-666.
6.    Gerold M. Complexation and Cyclodextrins. Encyclopedia of Pharmaceutical Technology by Marcel Dekkar; 2002; 531-558.
7.    Szejtli J. Cyclodextrin properties and applications. Drug Investigation, 1990: (Suppl 4): 11-21.
8.    Thorsteinn L, Marcus EB. Pharmaceutical Application of Cyclodextrins.Journal of Pharmaceutical Sceince. October 1996; volume 85, number 10.
9.    Handbook of Pharmaceutical Excipients, 2nd Edition (Wade A, Isweller P eds), The American Pharmaceutical Association, Washington, 1994: 145-147.
10.    Chowdhary KPR. Cyclodextrin as Drug carriers. The Indian Pharmacist. October 2003; 11-14.
11.    Bekers O, Uijtendaal EV, Beijnen JH, Bult A. and Underberg WJM. Cyclodextrins in the Pharmaceutical Field. Drug Development and Industrial Pharmacy. 1991; 17(11): 1503-1549.
12.    Thosteinn L, Marcus E, Mar M. Role of cyclodextrins in improving oral drug delivery. AM J Drug Dellv 2004;2 (4):1.
13.    Alfred Martin. Complexation and Protein Binding. Physical Pharmacy, 4th Edition, Waverly International, 428 East Preston Street, Maryland, USA; 1993; 258-260.
14.    Patel VP, Parikh RK, Gohel MC, Desai TR et al. Int. J PharmSci 2011; 2(1): 161-173
15.    Lachmann L, Herbert A Liberman, Joseph L Kanig. Kinetic Principles and stability testing, Chapter 26. In; Theory and Practice of Industrial Pharmacy, Varghese Publishing House, 1987: P – 767.
16.    Rajewski RA, Stella VJ. Pharmaceutical applications of cyclodextrins 2. In vivo drug delivery. J. Pharm. Sci., 1996; 85: 1142-1169.
17.    Baboota S, Kohli K, Ali J, Ahuja A. Cyclodextrins and their applications in biotechnology. The Indian Pharmacist. 2004 July;13-16.
18.    Deelip D, Boddu SHS, Magar M. Studies on the preparation, characterization and solubility of β-cyclodextrin-satranidazole inclusion complexes. Indian J Pharm Edu Res 2006 Oct-Dec; 40(4): 232-36.
19.    Reddy MN, Rehana T, Ramakrishna S, Chowdary KPR, Diwan PV.β- cyclodextrin complexes of celecoxib: Molecular-modeling, characterization and dissolution studies. AAPS Pharm Sci Tech 2004; 6(1): Artcle 7: 1-9.
20.    Sanoferjan AM, Swamy NGN, Mahesh S, Murthy SN. Formulation and evaluation of β-cyclodextrin complexes of tenoxicam. Indian J Pharm Sci 2000 Mar-Apr; 62(3): 119-21.
21.    Nath BS, Shivkumar HN. A 23 factorial studies on factors influencing meloxicam β-cyclodextrin complexation for better solubility. Indian J Pharm Sci 2000 Mar-Apr; 62(3): 129-32.
22.    Parikh RK, Mansuri NS, Gohel MC, Soniwala MM. Dissolution enhancement of nimesulide using complexation and salt formation techniques. Indian Drugs 2005 Mar; 42(3): 149-54.
23.    Tenjara S, Puranajoti P, Kasina R, Mandal T. Preparation, characterization and evaluation of miconazole-cyclodextrin complexes for improved oral and topical delivery. J Pharm Sci 2000 Jun; 87(4): 425-29.
24.    Shyale S, Chowdary KPR, Krishnaiah YSR. Development of colon- targetedalbendazole-cyclodextrin-complex drug delivery systems. Drug Dev Res 2005 Sep; 65(2): 76-83.
25.    Chowdary KPR, Kamalakara RG. Controlled release of nifedipine from mucoadhesive tablets of its inclusion complexes with β-cyclodextrin. Pharmazie 2003 Oct; 58(10): 721-24.
26.    Chowdary KPR, Srinivas SV. Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl β-cyclodextrin. AAPS Pharm Sci Tech 2006; 7(3): Article 79: E1-E6.
27.    Patel VP, Parikh RK, Gohel MC, Desai TR et al. Int. J PharmSci 2011; 2(1): 161-173
28.    Higuchi T and Connors KA. Phase-solubility techniques. Adva Anal Chem Instr. 1965; 4: 217-22.
29.    Fars K. Alanazi, Mahmoud El-Badry, Mahrous O. Ahmed and Ibrahim A. Alsarra. Sci Pharm 2007; 75: 63-79
30.    Nash RA. Pharmaceutical excipients .23 August 2005; 564-580.
31.    Rajputh SJ and Raj HA. Simultaneous spectroscopic estimation of ezetimibe and Simvastatin in tablet dosage form. Indian J Pharma sci 2007: Volume: 69 Issue:6 Page: 759-762.
32.    Thorsteinn L, Dagny H, Mar M. Evaluation of cyclodextrin solubilization of drugs. International Journal of Pharmaceutics 302 (2005) 18-28.
33.    Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methycellose. Advanced Drug Delivery Reviews 48 (2001)139-157.
34.    International Conference on Harmonization (ICH), Harmonized Tripartite guideline for stability testing of new drugs substances and products Q1A (R2) 2003 Aug.
35.    International Conference on Harmonization (ICH), Harmonized Tripartite guideline for stability testing of existing active substances and related finished products Q1A (R2) 2004 Mar.
36.    Punit S, Rajshree M, Yogesh R. Stability testing of pharmaceuticals- A global perspective. J Phar Res. 2007; 6(1): 1-9.
37.    Grimm W. Extension of The International Conference on Harmonization Tripartite guideline for stability testing of new drug substances and products to countries of climatic zones III and IV. Drug Dev Ind Pharm. 1998 Apr; 24(4): 313-25.
38.    Stability studies information: International Conference on Harmonization (ICH) Q1F. Stability data package for registration applications climatic zones. III and IV, June 2006.
39.    Monique WJ, Den Brok, Sabien C, Vander Schoot, Bastiaan Nuijen, Michel JX, Hillebrand, Jos H, Beijnen et al. 2-hydroxypropyl-β-cyclodexxtrin extracts 2-phenylphenol from silicone tubing. International Journal of Pharmecetics. 2004; 278: 303-309.
40.    Morten P, Jette J, Alex MS. Cyclodextrin inclusion complexes of miconazole and Econazole. Drug Development & Industrial Pharmacy. 1999; 25(4): 463- 470.
41.    Thorsteinn L, Mar M, Marcus EB. Self-Association of Cyclodextrins and Cyclodextrin complexes. J. Pharm. Sci., May 2004; 93(5):1091-1099.
42.    Vavia PR, Adhage NA. Inclusion complexation of Nimusulide with βCyclodextrins. Dug Development and Industrial Pharmacy. 1999; 25(4): 543-545.
43.    Han GC, Beom JL, Jeong HH, Kyung L, Kyung MP, Chul SY. et al. Terfenadine-β-cyclodextrin inclusion complex with anti-histaminic activity enhancement. Drug Development & Industrial Pharmacy. 2001; 27(8): 857-862.
44.    Veiga F, Teixeira-Dias JJC, Kedzierewicz F, Sousa A, Maincent P. Inclusion complexation of tolbutamide with β-cyclodextrin and hydroxypropyl-β- cyclodextrin. International Journal of Pharmaceutics. 1996; 129; 63-71.
45.    Jichao K, Vijay K, Dong Y, Priyanka RC, Raymond JH. Cyclodextrin complexation: Influence on the solubility, stability and cytotoxicity of compacthecin, an antineoplastic agent. European Journal of Pharmaceutical Sciences. 2002; 15: 163-170.
46.    Esclusa-Diaz MT, Guimaraens-Mfndez M, Pfrez-Marcos MB, Vila-Jato JL, Torres-Labandeira JJ. Characterization ketoconazole/ fl- and and in vitro dissolution behaviour of 2-hydroxypropyl-fl-cyclodextrin inclusion compounds. International Journal of Pharmaceutics. 1996; 143: 203-210.
47.    Mario J, Mira BL. Influence of hydroxylpropyl -β-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. European Journal of Pharmaceutical Science. 2004; 21: 251-260.
48.    Erem BL, Dogan, Murat S, Atilla H. Complexation behavior of antiestrogen drug tamoxifen citrate with natural and modified b-cyclodextrins Incl Phenom Macrocycl Chem. 2007; 57: 651-655.
49.    Josef P, Teruhiko H. Effects of ethanol on formation of inclusion complexes of hydroxypropyl cyclodextrins with testosterone. International Journal of Pharmaceutics. 1992; 80: 243-251.
50.    Nagesh B, William W, Christopher BR, Lakshmi PK Uday BK. Preparation of budesonide and indomethacin-hydroxypropyl-β-cyclodextrin complexes using a single step, organic solvent free super-critical fluid process. European Journal of Pharmaceutical Sciences. 2004; 23: 159-168.
51.    Sunil J, Casella R, Maher T. The physicochemical characteristics and bioavailability of indomethacin from β-cyclodextrin, hydroxy-ethyl β-cyclodextrin and hydroxyrpopyl-β-cyclodextrin complexes. International Journal of Pharmaceutics. 2004; 270: L 149-166.
52.    David D, Carolina M, Escobar L, Maria J, Bernad B. Study of the binding in an aqueous medium of inclusion complexes of several cyclodextrins involving Fenoprofen calcium. Drug Development & Industrial Pharmacy. 1999; 25(1): 107-110.
53.    Francisco V, Catarina F, Philippe M. Influence of the preparation method on the physicochemical properties of tolbutamide/ cyclodextrin binary system. Drug Development & Industrial Pharmacy. 2001; 27(6): 523-532.
54.    Francesca M, Paola M, Angela C, Francesco M, Andrea S. et al. Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long lasting topically acting antiglaucoma agents. J. Pharma. Sci., 2002; 91(10): 2211- 2219.
55.    Tayede PT, Vavia PR. Inclusion complexes of ketoprofen with β- Cyclodextrins: Oral Pharmacokinetics of ketoprofen in human. Indian J.Pharm.Sci, 2006; 68(2):164-170.
56.    Ann MS, Nguyen BN, Annectte BB. and Martin B. Effect of Hydroxy propyl β- cyclodextrin complexation and PH on solubility of Camtothecin. Int J Pharmaceutics. 2004; 284: 1-2, 61-68.
57.    Swati R, Sanjay KJ. Solubility enhancement of Celecoxib using β- cyclodextrin complexes. European Journal of Pharmaceutics and Biopharmacetics. 2004; 57(2):263-267.
58.    Brunella C, Giuseppe DR et al. Cyclodextrin-contenting poly (ethylineneoxide) tablets for the drug delivery of poorly soluble drugs: Potential as buccal delivery system. International Journal of Pharmaceutics. 2006; 319: 63-70.
59.    Kiran T, Nalini S, Ramakrishna S, Sadanandam M. Surface solid dispersion of glimepiride for Enhancement of dissolution rate. Int. J. Pharm Tech Res. 2009; 1(3): 822-831.
60.    Chaudhari MD, Sonawane RO, Zawar L, Nayak S, Bari SB. Solubility and dissolution enhancement of poorly water soluble glimepiride by using solid dispersion technique. Int J Pharm Pharm Sci. 2012; 4(5): 534-539.
61.    Wagh VT, Jagtap VA, Shaikh TJ, Nandedkar SY. Formulation and Evaluation of Glimepiride Solid Dispersion Tablets for Their Solubility Enhancement. J Adv Sci Res. 2012; 3(4): 36-41 36
63.    Moneghini M, Bellich B, Baxa P, Princivalle F. Int. J Pharmaceutics. 2008; 361: 125-130.

Recomonded Articles:

Author(s): Ulhas Balkrishna Hadkar, Poonam Rajesh Advani, Radhika Kishore Raheja

DOI: 10.5958/2231-5713.2017.00017.4         Access: Open Access Read More

Author(s): A.V.S. Ksheera Bhavani, A. Lakshmi Usha, Kayala Ashritha, E. Radha Rani

DOI: 10.52711/2231-5713.2021.00029         Access: Open Access Read More

Author(s): M. Kranthi Kumar Reddy, B. Narasimha Rao , K. Ravindra Reddy.

DOI:         Access: Open Access Read More

Author(s): Ulhas Balkrishna Hadkar, Munira Aunali Loliwala

DOI: 10.5958/2231-5713.2015.00016.1         Access: Open Access Read More

Asian Journal of Pharmacy and Technology (AJPTech.) is an international, peer-reviewed journal, devoted to pharmaceutical sciences...... Read more >>>

RNI: Not Available                     
DOI: 10.5958/2231–5713 

Recent Articles