Optimization and development of orodispersible films for ledipasvir and sofosbuvir through solid dispersion using Box-Behnken design

2021 ◽  
pp. 201-208
Author(s):  
Uday Kumar Thummala ◽  
Eswar Guptha Maddi ◽  
Prameela Rani Avula
Keyword(s):  
Solid Dispersions ◽  
Methyl Cellulose ◽  
Fixed Dose ◽  
Polyethylene Glycol 400 ◽  
Disintegration Time ◽  
Box Behnken Design ◽  
Orodispersible Films ◽  
Low Viscosity ◽  
Dose Combination ◽  
Formulation Parameters

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.

Optimization and Quality by Design Approach for Piroxicam Fast Dissolving Tablet Formulations Using Box-Behnken Design

2020 ◽  
Vol 15 (2) ◽  
pp. 152-165
Author(s):  
Harekrishna Roy ◽  
Sisir Nandi ◽  
Ungarala Pavani ◽  
Uppuluri Lakshmi ◽  
Tamma Saicharan Reddy ◽  
...  
Keyword(s):  
Quality By Design ◽  
Methyl Cellulose ◽  
Statistical Technique ◽  
Quadratic Model ◽  
Contour Plot ◽  
Compression Technique ◽  
Disintegration Time ◽  
Box Behnken Design ◽  
The Impact ◽  
The Relationship

Background: The present study deals with the formulation and optimization of piroxicam fast dissolving tablets and analyzes the impact of an independent variable while selecting the optimized formulation utilizing Quality by Design (QbD) and Box-Behnken Design (BBD). Methods: Seventeen formulations were prepared by direct compression technique by altering the proportion of cross carmellose sodium, spray dried lactose and hydro propyl methyl cellulose (HPMC K4M). The BBD statistical technique was used to optimize formulations and correlate the relationship among all the variables. Also, the powder mixture characteristics and tablet physiochemical properties such as hardness, friability, drug content, Disintegration Time (DT) and dissolution test were determined using 900 ml of 0.1N HCl (pH-1.2) at 37 ± 0.5°C. Results: Significant quadratic model and second order polynomial equations were established using BBD. To find out the relationship between variables and responses, 3D response surface and 2D contour plot was plotted. A perturbation graph was also plotted to identify the deviation of the variables from the mean point. An optimized formula was prepared based on the predicted response and the resulting responses were observed to be close with the predicted value. Conclusion: The optimized formulation with the desired parameter and formulation with variables and responses can be obtained by BBD and could be used in the large experiment with the involvement of a large number of variables and responses.

scholarly journals Formulation and Optimization of Monolithic Fixed-Dose Combination of Metformin HCl and Glibenclamide Orodispersible Tablets

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anteneh Belayneh ◽  
Fantahun Molla ◽  
Getu Kahsay
Keyword(s):  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Pill Burden ◽  
Compression Force ◽  
Disintegration Time ◽  
Peg 6000 ◽  
Ir Studies ◽  
Orodispersible Tablets ◽  
Swallowing Problems ◽  
Dose Combination

The treatment of type II DM involves the use of combination of drugs, especially at the chronic stage. However, the pill burden of this combination therapy combined with swallowing difficulties, occurring at a later stage of DM, has been the major challenge for successful treatment outcomes. This study was aimed at formulating and optimizing a monolithic fixed-dose combination (FDC) of metformin (MET) and glibenclamide (GLB) orodispersible tablets (ODTs) to overcome both the pill burden and swallowing problems. The FDC ODTs were prepared by the melt granulation technique using polyethylene glycol (PEG) 6000 as a binding agent and crospovidone as a superdisintegrant. In the preliminary study, the effects of sodium lauryl sulphate (SLS), PEG 6000, crospovidone, and compression force on friability, disintegration time, and drug release of tablets were investigated. The FT-IR studies showed that there were no incompatibilities between MET and GLB as well as within excipients. The preliminary studies revealed that PEG 6000 and compression force significantly affect both the friability and the disintegration time, while SLS and crospovidone only affect the disintegration time. Therefore, the effects of PEG 6000, crospovidone, and compression force were further studied and optimized using the central composite design. Accordingly, the most desirable optimal values were obtained at 3.82% of PEG 6000, 9.83% of crospovidone, and 10.6 kN compression force having a friability of 0.302% and a disintegration time of 18.7 seconds. From these results, it can be concluded that a monolithic FDC of MET and GLB ODTs having adequate mechanical strength and faster disintegration time was successfully formulated.

scholarly journals Applications of Alginates in the Design and Preparation of Orodispersible Dosage Forms

2021 ◽  
Author(s):  
Garba M. Khalid ◽  
Francesca Selmin
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Dosage Forms ◽  
Delivery Systems ◽  
Fixed Dose ◽  
Innovative Drug ◽  
Orodispersible Films ◽  
Dose Combination ◽  
Different Dimensions ◽  
Dysphagic Patients

Orodispersible dosage forms are attractive and innovative drug delivery systems that can fulfill individual patient needs, especially in children, elderly and among dysphagic patients. Indeed, they rapidly disperse in the mouth upon contact with the saliva without the need for water or munching. Examples of such dosage forms include orodispersible tablets (ODT), and orodispersible films (ODF). The ability to obtain ODF with different dimensions (sizes and thicknesses) makes them a suitable for personalized dosing of single or a fixed-dose combination of drugs in special patient populations. Several biopolymers are currently being exploited in the development of orodispersible dosage forms including alginates due to their versatility, availability, naturally occurring, and biosafety profile. This chapter provides an appraisal on the various applications of alginates in the preparations and their role on the properties of orodispersible dosage forms and highlights future perspectives of this very versatile biopolymer for these innovative drug delivery systems.

scholarly journals DESIGN AND STATISTICAL OPTIMIZATION OF MOUTH DISSOLVING SUBLINGUAL FILM OF FIXED DOSE COMBINATION OF DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE USING DESIGN OF EXPERIMENT IN THE TREATMENT OF NAUSEA AND VOMITING IN PREGNANCY

2018 ◽  
Vol 11 (12) ◽  
pp. 202
Author(s):  
Bobde Suwarna Suresh ◽  
Tank Hemraj M
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Nausea And Vomiting ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Pyridoxine Hydrochloride ◽  
Onset Of Action ◽  
Disintegration Time ◽  
Folding Endurance ◽  
Dose Combination

Objective: The present research aims at formulating a mouth dissolving sublingual film of fixed dose combination of doxylamine succinate (DS) and pyridoxine hydrochloride (PH) that would provide faster onset of action and hence relief from the condition of nausea and vomiting in pregnancy.Methods: Mouth dissolving films were prepared using a solvent casting technique. A 23 full-factorial design of eight formulations was set up with three independent variables: X1 - polymer 1 HPMC E15 concentration, X2 - polymer 2 HPMC E5 concentration, and X3 - plasticizer PEG 400 concentration. The responses, i.e., dependent variables measured for the study were Y1 disintegration time in seconds, Y2 tensile strength in kg/cm2, Y3 drug release in the percentage of DS, and Y4 drug release in the percentage of PH. All the formulations were evaluated for physicochemical parameters such as clarity, weight, thickness, folding endurance, surface pH, and content. The design expert software 11.0 trial version was used for statistical analysis of the responses.Results and Conclusion: All the film formulations were found to be transparent, non-tacky, and easily peelable having the satisfactory tensile strength and folding endurance. The concentration of polymer 1 and 2 was found to have a significant effect on disintegration time and drug release of mouth dissolving films. The best film formulation DP1 was found to have a disintegration time of 77.66 s and found to release 96.22% of DS and 95.43% of pyridoxine HCl in 21 min.

Enhanced delivery of fixed-dose combination of synergistic antichagasic agents posaconazole-benznidazole based on amorphous solid dispersions

2018 ◽  
Vol 119 ◽  
pp. 208-218 ◽  
Author(s):  
Camila Bezerra Melo Figueirêdo ◽  
Daniela Nadvorny ◽  
Amanda Carla Quintas de Medeiros Vieira ◽  
Giovanna Christinne Rocha de Medeiros Schver ◽  
José Lamartine Soares Sobrinho ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Amorphous Solid Dispersions ◽  
Dose Combination

Efficacy and safety of aclidinium/formoterol fixed-dose combination in patients with COPD, stratified by ICS use

Pneumologie ◽  
2016 ◽  
Vol 70 (S 01) ◽  
Author(s):  
ED Bateman ◽  
K Chapman ◽  
S Rennard ◽  
L Rekeda ◽  
M Moya ◽  
...  
Keyword(s):  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Dose Combination

135-OR: The Effect of Fixed-Dose Combination of Insulin Degludec and Liraglutide on Serum Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 135-OR
Author(s):  
ELENI PAPPA ◽  
CHRISTINA KOSTARA ◽  
CONSTANTINOS TELLIS ◽  
ALEXANDROS D. TSELEPIS ◽  
ELENI BAIRAKTARI ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lipoprotein Metabolism ◽  
Serum Lipoprotein ◽  
Insulin Degludec ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Dose Combination

Formulation and Optimization of Immediate Release Pellets of Antiplatelet Drugs Using Design of Experimentation

2017 ◽  
Vol 7 (04) ◽  
Author(s):  
Deshkar S. S. ◽  
Pore A. R.
Keyword(s):  
Platelet Aggregation ◽  
Drug Release ◽  
Peripheral Arterial Disease ◽  
Tissue Injury ◽  
Immediate Release ◽  
Arterial Disease ◽  
Fixed Dose ◽  
Disintegration Time ◽  
Peripheral Arterial ◽  
Pvp K30

Platelets play an important role in hemostasis during tissue injury, which blocks the defect and terminates blood loss. Platelet aggregation inhibitors are widely used in treatment of cardiovascular disorders and Peripheral arterial disease. Clopidogrel bisulphate and Cilostazol, are FDA approved BCS class II drugs, used in treatment of Platelet aggregation, peripheral arterial disease and intermittent claudication. The aim of the present study was to develop an immediate release pellets for combination of Clopidogrel bisulphate and Cilostazol using extrusion spheronization technique. The effects of spheronization speed(X1) and binder concentration (PVP K30) (X2), on size of pellets, disintegration time and drug release were studied using 32 full factorial design. The surface response and counter plot were drawn to facilitate an understanding of the contribution of the variables and their interaction. From the results, speed of spheronization of 1100 rpm and 5% concentration of PVP K30, were selected. In vitro drug release studies revealed more than 80% of clopidogrel bisulphate release and more than 75% of cilostazol release within 30 min of dissolution which complied with the pharmacopoeal limits. Film coated pellets did not show significant change in the drug release. DSC and FTIR studies revealed no interaction of drugs and excipient during pellet formulation. The pellet formulations of clopidogrel and cilostazol were found to be stable when stored at 40ºC±2ºC/ 75%RH±5%RH for 2 months. Conclusively, clopidogrel bisulphate and cilostazol pellet fixed dose combination could be successfully developed by design of experimentation and complied with pharmacopoeal limits.

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