Reutilization of Tacrolimus Extracted from Expired Prograf® Capsules: Physical, Chemical, and Pharmacological Assessment

Binkhathlan, Ziyad; Badran, Mohamed M.; Alomrani, Abdullah H.; Aljuffali, Ibrahim A.; Alghonaim, Mohammed; Al‐Muhsen, Saleh; Halwani, Rabih; Alshamsan, Aws

doi:10.1208/s12249-015-0433-7

Cited by 5 publications

(6 citation statements)

References 34 publications

(30 reference statements)

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“…The XRD data for TAC, PCL, PM, non-loaded, and TAC-loaded nanocapsules are shown in Figure 3. Regarding the pure drug, intense peaks of crystallinity between 2θ = 5 and 25 • were achieved as previously reported [39][40][41][42][43], while PCL proved its semicrystalline nature with characteristic peaks at 2θ of 21.45 and 23.73 • [30,44,45]. The PM shows crystallinity peaks coincident with those observed for the drug and the polymer.…”

Section: X-ray Diffraction (Xrd)supporting

confidence: 80%

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

et al. 2021

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Background: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. Methods: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. Results: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (−38 to −42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer–Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. Conclusions: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

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Section: X-ray Diffraction (Xrd)supporting

confidence: 80%

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

et al. 2021

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“…Tacrolimus was extracted from expired Prograf® 5 mg capsules (Batch # 7241), as previously described ( Binkhathlan et al, 2015 ). Methoxy PEO (M n 5,000), stannous octoate (∼95%), ε-caprolactone (97%), and THF (HPLC grade) were purchased from Sigma–Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Development and characterization of methoxy poly(ethylene oxide)- block -poly(ε-caprolactone) (PEO- b -PCL) micelles as vehicles for the solubilization and delivery of tacrolimus

Ali

Farah

Binkhathlan

2017

Saudi Pharmaceutical Journal

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Tacrolimus is a potent immunosuppressant; however, it suffers from several problems such as poor water solubility (4-12 μg/mL), low and variable oral bioavailability in patients, and narrow therapeutic window that could not be solved by the currently available formulation (Prograf®). Moreover, Prograf® contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions. Therefore, the aim of the present study was to investigate the potential of PEO--PCL polymeric micelles as alternative vehicles for the solubilization and delivery of tacrolimus. Four PEO--PCL block copolymers, with different molecular weights of PCL, were synthesized by ring opening polymerization of ε-caprolactone using methoxy polyethylene oxide (5,000 g mol) as initiator and stannous octoate as catalyst. Synthesized copolymers were characterized for their average molecular weights and polydispersity index by H NMR and gel permeation chromatography (GPC), respectively. Drug-free micelles of PEO--PCL were prepared through a co-solvent evaporation method using acetone as the organic co-solvent. Tacrolimus-loaded micelles were prepared using the same method with different initial amounts of drug. Prepared micelles were characterized for their mean diameter size and polydispersity of the micellar population by dynamic light scattering, and an HPLC assay was used to determine the encapsulation efficiency of tacrolimus. The average molecular weights of the synthesized copolymers were in the range of 8,400-28,000 with narrow distributions (PDI = 1.06-1.11). The copolymers were designated according to the degree of polymerization of ε-caprolactone, namely PEO--PCL, PEO--PCL, PEO--PCL, and PEO--PCL. All the prepared micelles were having diameters sizes less than 100 nm with narrow distributions. The highest drug solubilization was achieved with PEO--PCL, where the aqueous solubility of tacrolimus exceeded 300 μg/mL. Our results show a potential for PEO--PCL micelles as solubilizing vehicles for the delivery of tacrolimus.

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“…A reported HPLC method was modified and validated for dissolution and assay analysis of the formulations [ 30 ]. The HPLC consisted of Agilent 1260 series (Agilent Technologies, Wilmington, DE, USA) equipped with a quaternary pump, online degasser, column heater, autosampler, and UV/Vis detector.…”

Section: Methodsmentioning

confidence: 99%

Application of Sucrose Acetate Isobutyrate in Development of Co-Amorphous Formulations of Tacrolimus for Bioavailability Enhancement

et al. 2023

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The focus of the present work was to develop co-amorphous dispersion (CAD) formulations of tacrolimus (TAC) using sucrose acetate isobutyrate as a carrier, evaluate by in vitro and in vivo methods and compare its performance with hydroxypropyl methylcellulose (HPMC) based amorphous solid dispersion (ASD) formulation. CAD and ASD formulations were prepared by solvent evaporation method followed by characterization by Fourier transformed infrared spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), dissolution, stability, and pharmacokinetics. XRPD and DSC indicated amorphous phase transformation of the drug in the CAD and ASD formulations, and dissolved more than 85% of the drug in 90 min. No drug crystallization was observed in the thermogram and diffractogram of the formulations after storage at 25 °C/60% RH and 40 °C/75% RH. No significant change in the dissolution profile was observed after and before storage. SAIB-based CAD and HPMC-based ASD formulations were bioequivalent as they met 90% confidence of 90–11.1% for Cmax and AUC. The CAD and ASD formulations exhibited Cmax and AUC 1.7–1.8 and 1.5–1.8 folds of tablet formulations containing the drug’s crystalline phase. In conclusion, the stability, dissolution, and pharmacokinetic performance of SAIB-based CAD and HPMC-based ASD formulations were similar, and thus clinical performance would be similar.

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Reutilization of Tacrolimus Extracted from Expired Prograf® Capsules: Physical, Chemical, and Pharmacological Assessment

Cited by 5 publications

References 34 publications

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

Development and characterization of methoxy poly(ethylene oxide)- block -poly(ε-caprolactone) (PEO- b -PCL) micelles as vehicles for the solubilization and delivery of tacrolimus

Application of Sucrose Acetate Isobutyrate in Development of Co-Amorphous Formulations of Tacrolimus for Bioavailability Enhancement

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