Author(s): Uday Kumar Thummala, Eswar Guptha Maddi, Prameela Rani Avula

Email(s): udaykumar.chowdary16@gmail.com , meguptas@gmail.com , drapr64@gmail.com

DOI: 10.52711/0975-4377.2021.00036   

Address: Uday Kumar Thummala1,2*, Eswar Guptha Maddi3, Prameela Rani Avula4
1Associate Professor, Aditya College of Pharmacy, Surampalem, Kakinada, Andhra Pradesh, India.
2Research Scholar, School of Pharmacy, JNT University Kakinada, Kakinada, Andhra Pradesh, India.
3Sir CR Reddy College of Pharmaceutical Sciences, Eluru, Andhra Pradesh, India.
4University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India.
*Corresponding Author

Published In:   Volume - 13,      Issue - 3,     Year - 2021


ABSTRACT:
The fixed dose combination of ledipasvir (LDV) and sofosbuvir (SBV) is approved by USFDA in 2014 for the treatment of Hepatitis C virus infection and is available in the form of tablets. In the present work, the principal aim is to explore orodispersible films type dosage form to impart its characteristic advantages to these poorly soluble drugs so as to improve their bioavailability and ease of administration. Solid dispersions with low viscosity grade methyl cellulose A 15-LV (MC A 15-LV) at different ratios with LDV and SBV were prepared and evaluated to check their ability in improving the solubility of the drugs. The best drug to polymer ratio was selected to develop the films, using other excipients including plasticizer and superdisintegrant. Solvent casting method was used to develop the films. Three formulation parameters were selected as independent factors viz. thickness of the film (50-150 µm), concentration of superdisintegrant (sodium starch glycolate 6-10%) and concentration of plasticizer (polyethylene glycol 400, 10-20%). Disintegration time (DT), time for 90% dissolution (T90%) of LDV and time for 90% dissolution of SBV were taken as the response variables. The experiment was designed using Box-Behnken design. Among the polymers, MC A 15-LV produced maximum solubility at 1:2 ratio. The films obtained were found to have good tensile strength and % elongation with disintegration times in the range of 43-162 sec. The T90% values for LDV and SDV were found to be in the range of 8.4-21.2 min and 7.2-18.4 respectively. All the three formulation factors were found to have significant effect on the three responses. The optimum formulation was identified at 100 µm thickness, 10% superdisintegrant and 20% plasticizer which showed DT of 89 sec with T90% values of 8.4 min and 7.2 min for LDV and SBV respectively. The rapid disintegration and dissolution of the films signified that the set objective was achieved.


Cite this article:
Uday Kumar Thummala, Eswar Guptha Maddi, Prameela Rani Avula. Optimization and development of orodispersible films for ledipasvir and sofosbuvir through solid dispersion using Box-Behnken design. Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; 13(3):201-8. doi: 10.52711/0975-4377.2021.00036

Cite(Electronic):
Uday Kumar Thummala, Eswar Guptha Maddi, Prameela Rani Avula. Optimization and development of orodispersible films for ledipasvir and sofosbuvir through solid dispersion using Box-Behnken design. Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; 13(3):201-8. doi: 10.52711/0975-4377.2021.00036   Available on: https://rjpdft.com/AbstractView.aspx?PID=2021-13-3-7


REFERENCES:
1.    Abegel A et. al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis. 2016 Apr; 16(4): 459-64. doi: 10.1016/S1473-3099(15)00529-0
2.    Rezaee-Zavareh MS et. al. Combination of ledipasvir and sofosbuvir for treatment of hepatitis c virus genotype 1 infection: Systematic review and meta-analysis. Annals of Hepatology. 2017 Mar-Apr; 16(2): 188-97. Doi: 10.5604/16652681.1231577.
3.    German P. et al. Clinical pharmacokinetics and pharmacodynamics of ledipasvir/sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis C. Clinical Pharmacokinetics. 2016 May 18; 55: 1337-51. doi: 10.1007/ s40262-016-0397-0
4.    Srikar G et. al. Formulation optimization and characterization of amlodipine oral disintegrating tablets prepared by co-grinding technique. Der Pharmacia Lettre. 2013; 5(4): 335-43.
5.    Ahirwar Varsha, Khushwant S. Yadav, Shailendra Bindaiya. Formulation development and evaluation of fast dissolving films of oloptadine HCl. Asian Journal of Research in Pharmaceutical Sciences. 2021; 11(2): 103-8. doi: 10.52711/2231-5659.2021-11-2-2.
6.    Thakur S, Tyagi LK. Orodispersible films and their patent technology's as a novel drug delivery systems. International Journal of Pharmaceutical Sciences Review and Research. 2019 Sept-Oct; 58(1): 52-60
7.    Khan QU et. al.  Development and characterization of orodispersible film containing cefixime trihydrate. Drug Development and Industrial Pharmarmacy. 2020 Dec; 46(12): 2070-2080. doi: 10.1080/03639045.2020.1843477.
8.    Ahmad A et. al.  Development and Evaluation of Orodispersible Films by Solvent Casting Method Using Eletriptan Hydrobromide as a Model Drug. Latin American Journal of Pharmacy. 2020; 39(10): 1951-6.
9.    Raza SN et. al.  Formulation and evaluation of mouth dissolving films of Losartan potassium using 32 factorial design. International Journal of Pharmaceutical Sciences and Research. 2019; 10(3): 1402-11. doi: 10.13040/IJPSR.0975-8232.10(3).1402-11.
10.    Guntaka PCR, Lankapalli S. A comparative study of ledipasvir solid dispersion technique using spray drying and hot-melt extrusion. International Journal of Pharmaceutical Sciences and Research. 2018; 9(12): 5145-54.
11.    Mogal SA et. al.  Solid dispersion technique for improving solubility of some poorly soluble drugs. Der Pharmacia Lettre. 2012; 4(5): 1574-86.
12.    Saker R et. al.  Preparation and evaluation of nifedipine solid dispersions. Research Journal of Pharmacy and Technology. 2020; 13(9): 4148-4152. doi: 10.5958/0974-360X.2020.00732.5.
13.    Thummala UK et. al.  Estimation of ledipasvir and sofosbuvir by Vierdot’s method in bulk and dosage forms. International Journal of Pharmacy and Biological Sciences. 2018 Apr-Jun; 8(2): 35-42.
14.    Pushkarna N et. al.  Binary Solid Dispersions of Telmisartan using natural modified Neem Gum: Development and Characterization. Research Journal of Pharmacy and Technology. 2019; 12(9): 4387-93. doi:10.5958/0974-360X.2019.00754.6.
15.    Lee Y et. al.  Orally disintegrating films focusing on formulation, manufacturing process, and characterization. Journal of Pharmaceutical Investigation. 2017; 47: 183–201. doi:10.1007/ s40005-017-0311-2.
16.    Sanyang ML et. al.  Effect of plasticizer type and concentration on physical properties of biodegradable films based on sugar palm (Arenga pinnata) starch for food packaging. Journal of Food Science and Technology. 2016 Jan; 53(1): 326–36. doi:10.1007/ s13197-015-2009-7.
17.    Zhang L et. al.  Impact of super-disintegrants and film thickness on disintegration time of strip films loaded with poorly water soluble drug microparticles. Journal of Pharmaceutical Science. 2018 Aug; 107(8): 2107-18. doi:10.1016/j.xphs.2018.04.006.
18.    Swamy SK et. al.  Effect of Various Super Disintegrants on the Drug Release Profile of Orally Disintegrating Tablets. Asian Journal of Pharmacy and Technology. 2016; 6(2): 99-105. doi:10.5958/2231-5713.2016.00014.3.
19.    Roy A et. al.  Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets. Saudi Pharmaceutical Journal. 2009; 17: 233-41 doi:10.1016/j.jsps.2009.08.004.
20.    Grandhi S et. al.  Voriconazole solid lipid nanoparticles: Optimization of formulation and process parameters. Research Journal of Pharmacy and Technology. 2018 Jul; 11(7): 2829-35. doi:10.5958/0974-360X.2018.00522.X.
21.    Vieira MGA et. al.  Natural-based plasticizers and biopolymer films: A review. European Polymer Journal. 2011; 47: 254-63. doi:10.1016/j.eurpolymj.2010.12.011.
22.    Aguirre A et. al.  Properties of triticale protein films and their relation to plasticizing–antiplasticizing effects of glycerol and sorbitol Industrial Crops and products. 2013 Oct; 50: 297-303. doi: 10.1016/j.indcrop.2013.07.043.

Recomonded Articles:

Author(s): Gopal Rao M., M. A. Amutha Gnana Arasi, S. Jayaprakash, M. Arun Kumar, P. Kavitha

DOI:         Access: Open Access Read More

Author(s): Swapnil T. Deshpande, P. S. Vishwe, Rohit D. Shah, Swati S. Korabu, Bhakti R. Chorghe, DG Baheti

DOI:         Access: Open Access Read More

Author(s): Dipti G. Phadtare, Amol R. Pawar, R.B. Saudagar, Govind K.Patil

DOI: 10.5958/0975-4377.2017.00002.7         Access: Open Access Read More

Author(s): Yamunappa, Ravi Kumar, Pooja Shetty, Prathibha Suvarna, Narayana Swamy VB

DOI: 10.5958/0975-4377.2016.00012.4         Access: Open Access Read More

Author(s): Simila Madathil, RaviKumar, Anju Govind, Mercy Mathew, Narayana Swamy VB

DOI: 10.5958/0975-4377.2016.00013.6         Access: Open Access Read More

Author(s): Kritika Kanoujia, Chandraprabha Dewangan, Ayushi Masih, Dipti Sinha, Divya Oraon, Manisha Jaiswal, Monika Sahu, Ranjeeta Kumari, Sapna Pradhan, Ravi Suman, Rajkishan Dewangan, Roman Banjare, Pradeep Paikra, Mukesh Rawtiya, Mukta Agrawal, Ajazuddin, D. K. Tripathi, Amit Alexander

DOI: 10.5958/0975-4377.2018.00015.0         Access: Open Access Read More

Author(s): Isha Shah, Nensi Raytthatha, Jigar Vyas, Umesh Upadhyay

DOI: 10.52711/0975-4377.2021.00039         Access: Open Access Read More

Author(s): Chirag A. Patel, Priyal R. Patel, Dhrubo Jyoti Sen,Jayvadan K. Patel

DOI:         Access: Open Access Read More

Author(s): Patil Namrata D., Gondkar S.B., Saudagar R.B.

DOI: 10.5958/0975-4377.2016.00033.1         Access: Open Access Read More

Author(s): Sayad Basha.K, Sheema Nafees. S, Nethravani. G, Thirumalesh Naik S.B

DOI: 10.5958/0975-4377.2016.00015.X         Access: Open Access Read More

Author(s): Varsha R. Sandhan, S.B. Gondkar, R. B. Saudagar

DOI:         Access: Open Access Read More

Author(s): Hardik B. Rana, Kajol Patel, Mansi Dholakia, Vaishali T. Thakkar, Mukesh C. Gohel, Tejal R. Gandhi

DOI: 10.5958/0975-4377.2017.00006.4         Access: Open Access Read More

Author(s): Ashok Thulluru, K. Saravanakumar, Ch. S. Phani Kumar, Nawaz Mahammed, D. Sreeja, G. Bhuvanesh, N. Vamsi Chowdary, Nayeema Khowser Shaik

DOI: 10.5958/0975-4377.2019.00049.1         Access: Open Access Read More

Author(s): Swati Talokar, Rohan R Vakhariya, A.R Dhole

DOI: 10.5958/0975-4377.2017.00005.2         Access: Open Access Read More

Author(s): Swapnali A. Mohite, R. R. Vakhariya, S. K. Mohite, C. S. Magdum

DOI: 10.5958/0975-4377.2019.00017.X         Access: Open Access Read More

Author(s): Rajkumar Prasad Yadav, F. R. Sheeba

DOI: 10.52711/0975-4377.2021.00023         Access: Open Access Read More

Author(s): Debjit Bhowmik, Rishab Bhanot, Darsh Gautam, Parshuram Rai, K.P. Sampath Kumar

DOI: 10.5958/0975-4377.2017.00022.2         Access: Open Access Read More

Research Journal of Pharmaceutical Dosage Forms and Technology (RJPDFT) is an international, peer-reviewed journal, devoted to pharmaceutical sciences. ...... Read more >>>

RNI: Not Available                     
DOI: 10.5958/0975-4377 


Recent Articles




Tags