Formulation, Optimization and Evaluation of in-situ Gelling Liquid Oral Formulation of a Novel Antidiabetic Drug: Canagliflozin

Bhatta, Rohith Ganapathi; Rudragangaiah, Sadashivaiah; Kotappa, Satheesha Babu Birur

doi:10.5530/ijper.53.2s.56

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…DSC Studies DSC thermograms of pure API, physical mixture and dried nanosuspension are presented in Figure10. A sharp endothermic peak between 105 and 107 • C was observed on the thermogram of pure CFZ, which confirms the melting point as mentioned in both the technical data package and the literature[59]. CFZ melting point as an indicator of its crystal structure was not only visible in the PM's thermogram, but also in the CFZ nanosuspension.…”

supporting

confidence: 83%

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Pirincci Tok,

Mesut,

Güngör

et al. 2023

Bioengineering

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One of the crucial approaches to managing the low solubility and weak bioavailability of drugs is via nanocrystal technology. Through this technology, drug particles have an increased solubility and a faster dissolution rate due to high surface free energy, which requires an appropriate stabilizer(s) to prevent instabilities during the manufacturing process and storage of the nanosuspension. This study aimed to establish a scientific predictive system for properly selecting stabilizers or to reduce the attempts on a trial-and-error basis in the wet-milling method. In total, 42 experiments were performed to examine the effect of critical material attributes on the wettability of the drug, the saturation solubility in the stabilizer solutions or combinations thereof and the dynamic viscosity of stabilizer solutions. All data were evaluated by Minitab 19® and an optimization study was performed. The optimized formulation at a certain concentration of stabilizer combination was ground by Dyno Mill® with 0.3 mm beads for one hour. The optimized nanosuspension with a particle size of 204.5 nm was obtained in short milling time and offered 3.05- and 3.51 times better dissolution rates than the marketed drug product (Invokana® 100 mg) in pH 4.5 and pH 6.8 as non-sink conditions, respectively. The formulation was monitored for three months at room temperature and 4 °C. The parameters were 261.30 nm, 0.163, −14.1 mV and 261.50 nm, 0.216 and −17.8 mV, respectively. It was concluded that this approach might indicate the appropriate selection of stabilizers for the wet-milling process.

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confidence: 83%

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Pirincci Tok,

Mesut,

Güngör

et al. 2023

Bioengineering

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“…The floating time was evaluated by checking the time required for the in situ gel to be afloat on the surface of the gastric fluid at pH 1.2 (floating lag time). The duration of time the preparation stayed afloat on the medium's surface (duration of floating) was recorded [38].…”

Section: Buoyancy Studiesmentioning

confidence: 99%

Design and development of sodium alginate/ carboxymethyl cellulose in situ gelling system for gastroretentive delivery of lisinopril

PATIL¹,

PATIL²,

BHARADE³

et al. 2023

jrp

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Lisinopril is a potent ACE (angiotensin-converting enzyme) inhibitor used to treat hypertension and congestive heart failure. It exhibits 25% of low bioavailability. Hence, in the current study, the major objective was to increase the gastric transient time of lisinopril and develop in situ gel formulation for better absorption and modulating release behavior of lisinopril. Different formulations of lisinopril were prepared by using gelling polymers such as Carboxymethyl cellulose (CMC), pectin, and calcium carbonate. Sodium citrate was used to prevent gelation outside the gastric environment. The formulation was studied using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) to interpret the interaction between drugsand polymers. For optimization of in situ gelling system 3 2 full factorial design was employed to study the effect of independent variables, the concentration of CMC (X1) and concentration of sodium alginate (X2), on the dependent variables viscosity, and % drug content. Formulation (F5) containing 1.25% of sodium alginate, and 0.75% of CMC showed good gelling ability. The composition F5 was optimized on the basis of viscosity (5.03 Pa.s), drug content (94.06±1.0%), and cumulative drug release (95±0.73%) at 12 h. Floating in situ gelling system improved bioavailability and gastric transit time of lisinopril. A stability study indicated the absence of any noticeable change in the formulation. Thus, in situ gel formulation is a promising approach for gastro-retentive sustained delivery of lisinopril. These results ensure that the developed system is an alternative to conventional drug delivery systems and can enhance patient compliance.

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“…Canagliflozin is soluble in many organic solvents (methanol, dimethyl sulfoxide) and insoluble in aqueous media and freely soluble in 0.75% w/v of SLS. [23,24] We selected 0.75% w/v of SLS as dissolution medium. Pellets equivalent to 100 mg of the drug were weighed and added in to it.…”

Section: Tan (θ) = H/rmentioning

confidence: 99%

“…Fourier transform spectroscopy analysis [24] The infrared spectra of the samples were obtained using a compact Fourier transform infrared spectrometry (FT-IR) spectrometer ALPHA II (BRUKER, Germany). 1-2 mg of fine solid powder of sample was directly analysed over the region 400 to 4000 cm -1 in the instrument.…”

Section: Tan (θ) = H/rmentioning

confidence: 99%

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A recent solidification approach for nanosuspension: formulation, optimisation and evaluation of canagliflozin immediate release pellets

Patel¹,

Patel²

2022

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Introduction: Canagliflozin is a BCS class IV drug. Nanosuspension is known to enhance the saturation solubility and dissolution rate of poorly soluble drugs owing to the increased surface area of nanosized particles. Aim: In the present study, we aimed to improve the dissolution characteristics of a poorly water-soluble drug canagliflozin by nanosuspension formulation and stability of this solubility enhancing system - nanosuspension can be improved by converting them into solidified forms as immediate release pellets. Materials and methods: Canagliflozin nanosuspension was formulated using the media milling method. Poloxamer 407 was used to stabilise nanosuspension. Prepared nanosuspensions were subjected to the characterisation of particle size, polydispersity index (PDI), and drug content. Optimised nanosuspension (NS1) was solidified by converting into immediate release pellets: as improved stability, where canagliflozin nanosuspension was used as a binder. Pellets were prepared by +extrusion-spheronization technique using microcrystalline cellulose (MCC) as pelletizing aid and sodium starch glycolate as super disintegrant. Different important process parameters e.g. concentration of sodium starch glycolate (A), spheronization speed (B) and spheronization time (C) were investigated by 23 factorial design to accomplish desired disintegration time (R1) and drug release at 10 min (R2). Results: The optimised nanosuspension had 120.5 nm particle size, 99.14% drug content and the optimised immediate release pellets (PF5) disintegrated within 23.29 second, and had 99.11% drug content. In vitro dissolution studies showed 89.59% drug release within 10 min in 0.75% w/v SLS. Scanning electron microscopy (SEM) confirmed uniform and spherically shaped pellets. Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) analysis reveal no significant interaction between drug and excipients. Conclusions: It can be concluded from the findings of this study that the formulation of nanosuspension and its use as a binder in the formulation of immediate release pellets should be investigated further in order to improve the dissolution rate and formulation stability.

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Formulation, Optimization and Evaluation of in-situ Gelling Liquid Oral Formulation of a Novel Antidiabetic Drug: Canagliflozin

Cited by 6 publications

References 11 publications

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method

Design and development of sodium alginate/ carboxymethyl cellulose in situ gelling system for gastroretentive delivery of lisinopril

A recent solidification approach for nanosuspension: formulation, optimisation and evaluation of canagliflozin immediate release pellets

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