Author(s): Neelam Sharma, Neha Kanojia, Sukhbir Singh, Anita Antil


DOI: 10.52711/0974-360X.2022.00954   

Address: Neelam Sharma1, Neha Kanojia2,3, Sukhbir Singh1*, Anita Antil3,4
1Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana - Ambala, Haryana, India 133207.
2Chitkara University School of Basic Sciences, Chitkara University, Himachal Pradesh, India.
3Chitkara College of Pharmacy, Chitkara University, Punjab, India.
4Janta College of Pharmacy, Butana, Sonipat.
*Corresponding Author

Published In:   Volume - 15,      Issue - 12,     Year - 2022

The objective of this research work was to develop solid dispersion of Fluvastatin sodium (FLS-SD) by solvent evaporation technique for dissolution enhancement of Fluvastatin sodium (FLS). Furthermore, central composite design (CCD) was applied for studying the effect of drug: polymer (w/w) (X1) and surfactant concentration (% w/v) (X2) on dependent variables T50% (Minutes) (Y1), Q90(%) (Y2) and percentage drug content (Y3). Thirteen experimental runs were performed as per CCD design layout and analyzed. The model was exceptional fitted in quadratic model as indicated by lack of fit of p-value more than 0.05. An optimized FLS-SD composition having 0.998 desirability function was explored using Design-Expert software. The theoretical values of t50%, Q90 and % drug content for optimized FLS-SD given by software were 23 min, 94.289% and 88.515%, respectively. The percentage cumulative drug release from FLS, physical mixture and FLS-SD was found 25.43%, 27.54%, and 93.6% within 2 hour which demonstrated superior and significant dissolution enhancement of FLS (*p < 0.05). The r2 for the Zero-order, First-order, Korsmeyer-peppas (K-P), and Higuchi models for FLS-SD were 0.8336, 0.7594, 0.9539 and 0.9234, respectively. K-P model was found superior (y = 0.426x +1.1259, r2 = 0.9539) and ‘n’ value was 0.426(n <0.45) which revealed fickian drug release from FLS-SD. This research work concluded that solid dispersion formulation by solvent evaporation technique could be successfully utilized for dissolution enhancement of BCS class II drug.

Cite this article:
Neelam Sharma, Neha Kanojia, Sukhbir Singh, Anita Antil. Application of Central Composite Design for Formulation and Optimization of Solid Dispersion for Dissolution Rate Enhancement of BCS Class II Drug. Research Journal of Pharmacy and Technology 2022; 15(12):5659-4. doi: 10.52711/0974-360X.2022.00954

Neelam Sharma, Neha Kanojia, Sukhbir Singh, Anita Antil. Application of Central Composite Design for Formulation and Optimization of Solid Dispersion for Dissolution Rate Enhancement of BCS Class II Drug. Research Journal of Pharmacy and Technology 2022; 15(12):5659-4. doi: 10.52711/0974-360X.2022.00954   Available on:

1.    Ndlovu ST. Ullah N. Khan S. Ramharack P. Soliman M. de Matas M. Shahid M. Sohail M. Imran M. Shah SW. Hussain Z. Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction. Drug Delivery and Translational Research 2019; 9(1): 284-297.
2.    Martin B. Seguin J. Annereau M. Fleury T. Lai-Kuen R. Neri G. Lam A. Bally M. Mignet N. Corvis Y. Preparation of parenteral nanocrystal suspensions of etoposide from the excipient free dry state of the drug to enhance in vivo antitumoral properties. Scientific Reports 2020; 10(1): 1-3.
3.    Mahalapbutr P. Wonganan P. Charoenwongpaiboon T. Prousoontorn M. Chavasiri W. Rungrotmongkol T. Enhanced solubility and anticancer potential of mansonone G by β-cyclodextrin-based host-guest complexation: A computational and experimental study. Biomolecules 2019; 9(10): 545.
4.    Taghavi Kevij H. Mohammadian M. Salami M. Complexation of curcumin with whey protein isolate for enhancing its aqueous solubility through a solvent‐free pH‐driven approach. Journal of Food Processing and Preservation 2019; 43(12): e14227.
5.    Alshehri S. Imam SS. Altamimi MA. Hussain A. Shakeel F. Elzayat E. Mohsin K. Ibrahim M. Alanazi F. Enhanced dissolution of luteolin by solid dispersion prepared by different methods: Physicochemical characterization and antioxidant activity. ACS Omega 2020; 5(12): 6461-6471.
6.    Kim SJ. Lee HK. Na YG. Bang KH. Lee HJ. Wang M. Huh HW. Cho CW. A novel composition of ticagrelor by solid dispersion technique for increasing solubility and intestinal permeability. International Journal of Pharmaceutics 2019; 555: 11-18.
7.    Jaydip B. Dhaval M. Soniwala MM. Chavda J. Formulation and optimization of liquisolid compact for enhancing dissolution properties of efavirenz by using DoE approach. Saudi Pharmaceutical Journal 2020; 28(6): 737-745.
8.    Thakkar HP. Vasava D. Patel AA. Dhande RD. Formulation and evaluation of liquisolid compacts of itraconazole to enhance its oral bioavailability. Therapeutic Delivery 2020; 11(2): 83-96.
9.    Chaudhari KS. Akamanchi KG. Novel bicephalous heterolipid based self-microemulsifying drug delivery system for solubility and bioavailability enhancement of efavirenz. International Journal of Pharmaceutics 2019; 560: 205-218.
10.    Sawatdee S. Atipairin A. Sae Yoon A. Srichana T. Changsan N. Suwandecha T. Formulation development of albendazole-loaded self-microemulsifying chewable tablets to enhance dissolution and bioavailability. Pharmaceutics 2019; 11(3): 134.
11.    Naqvi A. Ahmad M. Minhas MU. Khan KU. Batool F. Rizwan A. Preparation and evaluation of pharmaceutical co-crystals for solubility enhancement of atorvastatin calcium. Polymer Bulletin 2019; 1-21.
12.    Ammanage A. Rodriques P. Kempwade A. Hiremath R. Formulation and evaluation of buccal films of piroxicam co-crystals. Future Journal of Pharmaceutical Sciences 2020; 6: 1.
13.    Choi JS. Park JW. Park JS. Design of Coenzyme Q10 solid dispersion for improved solubilization and stability. International Journal of Pharmaceutics 2019; 572: 118832.
14.    Colombo M. de Lima Melchiades G. Michels LR. Figueiró F. Bassani VL. Teixeira HF. Koester LS. Solid dispersion of kaempferol: Formulation development, characterization, and oral bioavailability assessment. AAPS PharmSciTech 2019; 20(3): 1-9.
15.    Luu TD. Lee BJ. Tran PH. Tran TT. Modified sprouted rice for modulation of curcumin crystallinity and dissolution enhancement by solid dispersion. Journal of Pharmaceutical Investigation 2019; 49(1): 127-134.
16.    Zi P. Zhang C. Ju C. Su Z. Bao Y. Gao J. Sun J. Lu J. Zhang C. Solubility and bioavailability enhancement study of lopinavir solid dispersion matrixed with a polymeric surfactant-Soluplus. European Journal of Pharmaceutical Sciences 2019; 134: 233-245.
17.    Kim SJ. Lee HK. Na YG. Bang KH. Lee HJ. Wang M. Huh HW. Cho CW. A novel composition of ticagrelor by solid dispersion technique for increasing solubility and intestinal permeability. International Journal of Pharmaceutics 2019; 555: 11-18.
18.    Kwon J. Giri BR. Song ES. Bae J. Lee J. Kim DW. Spray-dried amorphous solid dispersions of atorvastatin calcium for improved supersaturation and oral bioavailability. Pharmaceutics 2019; 11(9): 461.
19.    Altamimi MA. Elzayat EM. Qamar W. Alshehri SM. Sherif AY. Haq N. Shakeel F. Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion. Saudi Pharmaceutical Journal 2019; 27(5): 629-636.
20.    Li J. Yang M. Xu WR. Enhanced oral bioavailability of fluvastatin by using nanosuspensions containing cyclodextrin. Drug Design, Development and Therapy 2018; 12: 3491-3499.
21.    Jagtap S. Magdum C. Jagtap R. Ameliorated Solubility and Dissolution of Flurbiprofen using Solubilizer Sepitrap 80 and Sepitrap 4000. Research Journal of Pharmacy and Technology 2021; 14(1): 21-27.
22.    Kolašinac N. Kachrimanis K. Homšek I. Grujić B. Đurić Z. Ibrić S. Solubility enhancement of desloratadine by solid dispersion in poloxamers. International Journal of Pharmaceutics 2012; 436(1-2): 161-170.  
23.    Ding Z. Wang L. Xing Y. Zhao Y. Wang Z. Han J. Enhanced oral bioavailability of celecoxib nanocrystalline solid dispersion based on wet media milling technique: formulation, optimization and in vitro/in vivo evaluation. Pharmaceutics 2019; 11(7): 328.
24.    Sharma N. Singh S. Laller N. Arora S. Application of central composite design for statistical optimization of trigonella foenum-graecum phytosome-based cream. Research Journal of Pharmacy and Technology 2020; 13(4): 1627-1632.
25.    Dutta S. Kulkarni PK. Shailesh T. Dissolution behavior of Olmesartan Medoxomil drug in Polymeric Micelles of Soluplus and Pluronic F127. Research Journal of Pharmacy and Technology 2021; 14(4): 2200-2204.
26.    Reddy N. Dugasani S. Nayakanti D. Solubility Promotion of Telmisartan by solid dispersions using Polymer combinations. Research Journal of Pharmacy and Technology 2021; 14(1): 280-284.
27.    Patel RP. Patel MM. Physicochemical characterization and dissolution study of solid dispersions of lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30. Pharmaceutical Development and Technology 2007; 12(1): 21-33.
28.    Shah M. Patel M. Development and Characterization of tadalafil solid dispersion using skimmed milk for improved the solubility and Dissolution release profile. Research Journal of Pharmacy and Technology 2020; 13(12): 6212-6217.
29.    Spandana B. Shashidher B. Dinesh S. Nagaraj B. Eletriptan hydrobromide Orodispersible tablets: Design, Development and In vitro characterization. Research Journal of Pharmacy and Technology 2020; 13(11): 5339-5344.
30.    Beena P. Krishnan AG. Ullas N. Pillai CS. Mathew SC. Salim S. Development and characterization of orally dissolving tablet of a poorly soluble antiemetic drug. Research Journal of Pharmacy and Technology 2021; 14(4): 2172-2178.
31.    Huang R. Han J. Wang R. Zhao X. Qiao H. Chen L. Li W. Di L. Zhang W. Li J. Surfactant-free solid dispersion of BCS class IV drug in an amorphous chitosan oligosaccharide matrix for concomitant dissolution in vitro-permeability increase. European Journal of Pharmaceutical Sciences 2019; 130: 147-155.
32.    De Oliveira Eloy J. Saraiva J. de Albuquerque S. Marchetti JM. Solid dispersion of ursolic acid in Gelucire 50/13: a strategy to enhance drug release and trypanocidal activity. AAPS PharmScitech 2012; 13(4): 1436-1445.
33.    Ghareeb MM. Abdulrasool AA. Hussein AA. Noordin MI. Kneading technique for preparation of binary solid dispersion of meloxicam with poloxamer 188. AAPS Pharmscitech 2009; 10(4): 1206-1215.  
34.    Ahuja N. Katare OP. Singh B. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.     European Journal of Pharmaceutics and Biopharmaceutics 2007; 65(1): 26-38.
35.    Khan AW. Kotta S. Ansari SH. Sharma RK. Ali J. Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by solid dispersion utilizing fourth generation carrier. Drug Development and Industrial Pharmacy 2015; 41(5): 772-779.
36.    Singh G. Pai RS. Devi VK. Optimization of pellets containing solid dispersion prepared by extrusion/spheronization using central composite design and desirability function. Journal of Young Pharmacists 2012; 4(3): 146-156.
37.    Sammour OA. Hammad MA. Zidan AS. Mowafy AG. QbD approach of rapid disintegrating tablets incorporating indomethacin solid dispersion. Pharmaceutical Development and Technology 2011; 16(3): 219-227.
38.    Shivakumar HN. Desai BG. Deshmukh G. Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology. Indian Journal of Pharmaceutical Sciences 2008; 70(1): 22.
39.    Taokaew S. Ofuchi M. Kobayashi T. Chitin biomass-nifedipine amorphous solid dispersion for enhancement of hydrophobic drug dissolution in aqueous media. Sustainable Chemistry and Pharmacy 2020; 17: 100284.
40.    Ata S. Rasool A. Islam A. Bibi I. Rizwan M. Azeem MK. Iqbal M. Loading of Cefixime to pH sensitive chitosan based hydrogel and investigation of controlled release kinetics. International Journal of Biological Macromolecules 2020; 155: 1236-1244.
41.    Sumalatha B. Babu DJ. Venkatanarayana A. Reddy PR. Sruthi PD. Experimental investigation on biosorption of chromium from aqueous solution using citrus limonium peel: Optimization of process parameters using central composite design. Research Journal of Pharmacy and Technology 2018; 11(12): 5253-5264.
42.    Yadav AV. Yadav VB. Improvement of Physicochemical properties of Mesalamine with Hydrophilic Carriers by Solid Dispersion (kneading) method. Research Journal of Pharmacy and Technology 2008; 1(4): 422-425.
43.    Tran P. Pyo YC. Kim DH. Lee SE. Kim JK. Park JS. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics 2019; 11(3): 132.
44.    Bodas DS. Ige PP. Central composite rotatable design for optimization of budesonide-loaded cross-linked chitosan–dextran sulfate nanodispersion: characterization, in vitro diffusion and aerodynamic study. Drug Development and Industrial Pharmacy 2019; 45(7): 1193-1204.
45.    Febriyenti F. Rahmi S. Halim A. Study of gliclazide solid dispersion systems using PVP K-30 and PEG 6000 by solvent method. Journal of Pharmacy and Bioallied Sciences 2019; 11(3): 262.
46.    Ali S. Yousaf AM. Raza SA. Shahzad Y. Khan IU. Mahmood T. Hussain T. Manzoor M. Riaz H. Jamshaid M. Preparation and in vitro characterization of polyvinylpyrrolidone-poloxamer polymeric synergy for oral drug delivery. Journal of Polymer Research 2019; 26(7): 1-7.
47.    Yoshihashi Y. Iijima H. Yonemochi E. Terada K. Estimation of physical stability of amorphous solid dispersion using differential scanning calorimetry. Journal of Thermal Analysis and Calorimetry 2006; 85(3): 689-692.
48.    Chawla A. Sharma P. Pawar P. Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: formulation, optimization and in vitro evaluation. Acta Pharmaceutica. 2012; 62(4): 529-545.
49.    Lavanya M. Chinna Eswaraiah M. Jaya S. Design, Development and In-vitro Characterization of Floating tablets of Propranolol hydrochloride. Research Journal of Pharmacy and Technology 2020; 13(11): 5088-5094.
50.    Parikh A. Kathawala K. Song Y. Zhou XF. Garg S. Curcumin-loaded self-nanomicellizing solid dispersion system: Part I: Development, optimization, characterization, and oral bioavailability. Drug Delivery and Translational Research 2018; 8(5): 1389-1405.
51.    Chen B. Wang X. Zhang Y. Huang K. Liu H. Xu D. Li S. Liu, Q. Huang J. Yao H. Lin X. Improved solubility, dissolution rate, and oral bioavailability of main biflavonoids from Selaginella doederleinii extract by amorphous solid dispersion. Drug delivery 2020; 27(1): 309-322.
52.    Paradkar A. Ambike AA. Jadhav BK. Mahadik KR. Characterization of curcumin–PVP solid dispersion obtained by spray drying. International Journal of Pharmaceutics 2004; 271(1-2): 281-286.
53.    Zhao L. Wang L. Chang L. Hou Y. Wei C. Wu Y. Ginsenoside CK-loaded self-nanomicellizing solid dispersion with enhanced solubility and oral bioavailability. Pharmaceutical Development and Technology 2020; 25(9): 1127-1138.
54.    Tran PH. Tran TT. Lee KH. Kim DJ. Lee BJ. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility. Expert Opinion on Drug Delivery 2010; 7(5): 647-661.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available