Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 28:13:205-220.
doi: 10.2147/DDDT.S189105. eCollection 2019.

Formulation and clinical investigation of optimized vinpocetine lyoplant-tabs: new strategy in development of buccal solid dosage form

Tarek A Ahmed  1   2
Affiliations

Formulation and clinical investigation of optimized vinpocetine lyoplant-tabs: new strategy in development of buccal solid dosage form

Tarek A Ahmed. Drug Des Devel Ther. .

Abstract

Background: This work aimed to develop a new solid dosage formulation of vinpocetine (VPN) in the form of buccal freeze-dried pullulan-based tablets (lyoplant-tabs) loaded with physically modified drug binary system.

Methods: Different polyvinyl pyrrolidone (PVP) grades were studied to prepare an efficient VPN binary system characterized by enhanced equilibrium saturation solubility, solubilization efficiency, thermodynamic stability, and permeation through oral mucosal cell lines. The concentrations of pullulan and swelling-aid polymer that affect the quality attributes of lyoplant-tabs were optimized. Clinical pharmacokinetics study on human volunteers for the optimized lyoplant-tabs compared to marketed product was accomplished.

Results: A promising drug binary system with polyvinyl pyrrolidone vinyl acetate (PVP-VA64) utilizing the lyophilization technique was developed. Solid-state characterization confirmed transformation of VPN completely into the amorphous form. The concentrations of pullulan and swelling-aid polymer were significantly affecting the characteristics of the tablets. Compared to the commercial VPN tablets, pullulan-based buccal tablets demonstrated enhancement in the studied pharmacokinetic parameters with positive impact on the drug bioavailability.

Conclusion: These VPN lyoplant-tabs containing lyophilized PVP-VA64-VPN binary system can be considered as an alternative to currently available marketed tablets; however, further preclinical investigations using large number of volunteers are required.

Keywords: binary system; buccal tablets; clinical pharmacokinetics; freeze-drying; permeation; vinpocetin.

PubMed Disclaimer

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Phase solubility study diagram of VPN in aqueous solution of PVP-VA64 (A), and dissolution profile of VPN solid dispersion and pure drug (B). Abbreviations: PVP-VA64, polyvinyl pyrrolidone vinyl acetate; VPN, vinpocetine.
Figure 2
Figure 2
Differential scanning calorimetry thermograms of vinpocetine, polyvinyl pyrrolidone vinyl acetate, and lyophilized binary mixture.
Figure 3
Figure 3
Fourier transform infrared spectra of vinpocetine, polyvinyl pyrrolidone vinyl acetate, and lyophilized binary mixture.
Figure 4
Figure 4
X-ray powder diffraction patterns of pure vinpocetine and lyophilized binary mixture.
Figure 5
Figure 5
Standardized Pareto charts and estimated response surface plots for the effect of the studied factors on Y1 and Y2.
Figure 6
Figure 6
Plasma concentration–time curves for VPN after oral administration of commercial drug product and buccal formulations to human volunteers. Note: $Indicates significant difference (P<0.05) between groups I and II; *Indicates significant difference (P<0.05) between groups I and III; and #indicates significant difference (P<0.05) between groups II and III. Abbreviation: VPN, vinpocetine.
See this image and copyright information in PMC

References

    1. Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther. 2016;10:483–507. - PMC - PubMed
    1. Ahmed TA, El-Say KM. Transdermal film-loaded finasteride microplates to enhance drug skin permeation: two-step optimization study. Eur J Pharm Sci. 2016;88:246–256. - PubMed
    1. Bauduin P, Renoncourt A, Kopf A, Touraud D, Kunz W. Unified concept of solubilization in water by hydrotropes and cosolvents. Langmuir. 2005;21(15):6769–6775. - PubMed
    1. Ghebremeskel AN, Vemavarapu C, Lodaya M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int J Pharm. 2007;328(2):119–129. - PubMed
    1. Noolkar SB, Jadhav NR, Bhende SA, Killedar SG. Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions. AAPS Pharm Sci Tech. 2013;14(2):569–577. - PMC - PubMed