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Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation

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Abstract

Purpose

Investigate the possibility of delivering teriparatide orally using nanoemulsion.

Method

Teriparatide was allowed to interact with chitosan in the presence of HPβCD.The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology.Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4o C, 25o C and 40o C for three months.

Results

PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demostrated that the nanoemulsion is mostly stable at 4o C.

Conclusion

These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.

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Abbreviations

DLS:

Dynamic light scattering

FTIR:

Fourier transform infra red

HPβCD:

Hydroxypropyl beta cyclodextrin

LMWC:

Low molecular weight chitosan

OVX:

Ovariectomized rat

PEC:

Polyelectrolyte complex

PLGA:

Poly lactide glycolic acid

rhPTH:

Recombinant human para thyroid hormone

SC:

Subcutaneous

SGF:

Simulated gastric fluid

SIF:

Simulated intestinal fluid

DSC:

Differential scanning calorimetry

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Acknowledgments and Disclosures

The author wish to thanks Deanship of Research for providing the funding for this work (169/2012). The authors wish to thank Dr. Faisal Athamneh from Faculty of Chemistry, Jordan University of Science and Technology for his help. The authors are also thankful for Dr. Munther Al-Shami for his help in the pharmacokinetic statistics. The authors further wish to thank Dr. Adnan Badwan from the Jordanian Pharmaceutical Manufacturing Company (JPM) and Dr Adnan Dakkuri from Feris State University for providing valuable suggestions and guidance for this research.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Bashar M Altaani, Ammar M Almaaytah, Suha Dadou & Khouloud Alkhamis

  2. Currently Department of Pharmacy, Faculty of Pharmacy, Middle East University, Amman, Jordan

    Ammar M Almaaytah

  3. Department of Clinical Veterinary Medical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan

    Mousa H Daradka

  4. Department of Veterinary Pathology and Public Health, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan

    Wael Hananeh

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  1. Bashar M Altaani
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Altaani, B.M., Almaaytah, A.M., Dadou, S. et al. Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation. Pharm Res 37, 80 (2020). https://doi.org/10.1007/s11095-020-02793-0

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