Flaxseed Mucilage/Hydroxypropyl Methylcellulose and Sodium Alginate/Polyvinyl Alcohol Composite Bilayer Film as a Promising Drug Carrier for Periodontal Treatment

Abstract

Objectives: The present study focused on the formulation of mucoadhesive bilayer composite films for the treatment of periodontitis and evaluation of their physicochemical properties.

Materials and methods: The solvent casting technique was used to prepare films. The primary layer (D) was prepared with flaxseed and hydroxypropyl methylcellulose composite to sustain the release of doxycycline hyclate. The second layer (S) comprised sodium alginate and polyvinyl alcohol composite for faster release of clove oil. Both layers were combined to generate the bilayer film (B). All formulations were characterized further to obtain an optimized formulation.

Results: Attenuated total reflection-Fourier transform infrared radiation results showed intactness of drug and clove oil in the presence of excipients. The pH of the films was compatible with the periodontal cavity and the thickness was suitable for inserting into the cavity. The immediate release layer showed faster disintegration and swelling. The content of clove oil was above 80%. The rate of swelling of the primary layer was slow and drug content complied with the United States Pharmacopoeia. Scanning electron microscope analysis revealed intact, non-porous and smooth films. Films exhibited better mechanical strength and bioadhesiveness. Clove oil was released from the immediate release layer within 10 min, and doxycycline hyclate release was retarded to a minimum of up to 8 h in the primary layer as well as the bilayer. Formulation also had a significant effect on both Escherichia coli and Staphylococcus aureus.

Conclusion: In the current study, bilayers were successfully prepared and characterized. The optimized formulation can be effectively used for the treatment of periodontitis.

Keywords: HPMC; Periodontitis; clove oil; doxycycline hyclate; flax seed mucilage; polyvinyl alcohol; sodium alginate.

Figure 1

Schematic representation of the preparation of the primary layer HPMC: Hydroxypropyl methylcellulose

Figure 2

Schematic representation of the preparation of the secondary layer PVA: Polyvinyl alcohol

Figure 3

Schematic representation of the preparation of the bilayer film HPMC: Hydroxypropyl methylcellulose, PVA: Polyvinyl alcohol

Figure 4

a) Plain flaxseed mucilage-based doxycycline hyclate loaded film (D), b) Bilayer film (B) Composed of doxycycline hyclate in the primary layer and clove oil in the secondary layer

Figure 5

ATR-FTIR spectra of (A) doxycycline hyclate, (B) physical mixture of doxycycline hyclate, HPMC, and flaxseed, (C) formulation of primary layer (D1), (D) clove oil, and (E) formulation of S3 layer ATR: Attenuated total reflection, FTIR: Fourier transform infrared radiation, HPMC: Hydroxypropyl methylcellulose

Figure 6

Optical microscopy of bilayer film a, b and c showing a transverse sectional view of the bilayer film under 100x magnification power

Figure 7

Scanning electron microscopic images showing the surface morphology of bilayer film a) primary layer containing doxycycline hyclate, b) secondary layer containing eugenol, c) bilayer film B

Figure 8

Graph of CT3 texture analyzer of tensile strength: a) bilayer periodontal film formulation and b) single primary layer film

Figure 9

Swelling ratio of B and D films

Figure 10

Cumulative drug release profile of the immediate release film

Figure 11

Cumulative drug release profile of the B and D films

Figure 12

Antimicrobial activity of films: a. effect of primary layer film containing doxycycline hyclate (1) and clove oil (2) on Escherichia coli, b. effect of primary layer film containing doxycycline hyclate and clove oil on the zone of Staphylococcus aureus, c. effect