Formulation and Characterisation of Tetracycline-Containing Bioadhesive Polymer Networks Designed for the Treatment of Periodontal Disease

Jones, David S.; Lawlor, Michelle S.; Woolfson, A. David

doi:10.2174/1567201043480027

Cited by 20 publications

(10 citation statements)

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“…In this study the incorporation of tetracycline hydrochloride within gels composed of HEC significantly increased both the consistency and the mechanical properties. Considering the concentration of drug employed it is proposed that, in line with previous studies, 8,15 this increase in rheological structuring may be explained, at least in part, by the effect of dispersed solid on the resultant flow properties. Conversely, the rheological properties of HPMC gels were compromised by the presence of tetracycline hydrochloride, inferring that this therapeutic agent interfered with polymer-polymer interactions.…”

Section: Discussionsupporting

confidence: 70%

“…The incorporation of therapeutic agents into hydrophilic gels has been reported to affect the rheological prop- erties. For example, the dispersion of tetracycline hydrochloride into binary aqueous polymer networks significantly increased the viscoelastic properties 8,15 due to the effects of the dispersed solids on the overall semisolid character. In this study the incorporation of tetracycline hydrochloride within gels composed of HEC significantly increased both the consistency and the mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

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Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Jones

Muldoon

Woolfson

et al. 2005

J of Applied Polymer Sci

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ABSTRACT:Despite their widespread use, there is a paucity of information concerning the effect of storage on the rheological properties of pharmaceutical gels that contain organic and inorganic additives. Therefore, this study examined the effect of storage (1 month at either 4 or 37°C) on the rheological and mechanical properties of gels composed of either hydroxypropylmethylcellulose (3-5% w/w, HPMC) or hydroxyethylcellulose (3-5% w/w, HEC) and containing or devoid of dispersed organic (tetracycline hydrochloride 2% w/w) or inorganic (iron oxide 0.1% w/w) agents. The mechanical properties were measured using texture profile analysis whereas the rheological properties were analyzed using continuous shear rheometry and modeled using the Power Law model. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing polymer concentration (3-5% w/w) significantly increased the consistency, hardness, compressibility, and adhesiveness of the formulations due to increased polymer chain entanglement. Following storage (1 month at 4 and 37°C) the consistency and mechanical properties of additive free HPMC gels (but not HEC gels) increased, due to the time-dependent development of polymer chain entanglements. Incorporation of tetracycline hydrochloride significantly decreased and increased the rheological and mechanical properties of HPMC and HEC gels, respectively. Conversely, the incorporation of iron oxide did not affect these properties. Following storage, the rheological and mechanical properties of HPMC and HEC formulations were markedly compromised. This effect was greater following storage at 37 than at 4°C and, additionally, greater in the presence of tetracycline hydrochloride than iron oxide. It is suggested that the loss of rheological/mechanical structure was due to chain depolymerization, facilitated by the redox properties of tetracycline hydrochloride and iron oxide. These observations have direct implications for the design and formulation of gels containing an active pharmaceutical ingredient.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Jones

Muldoon

Woolfson

et al. 2005

J of Applied Polymer Sci

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show abstract

“…The kinetic models used were zero order, first order, Higuchi and Peppas equation. [28,31] The following plots were made: Q t vs. t (zero-order kinetic model); log (Q 0 -Q t ) vs. t (first-order kinetic model) and Q t vs. square root of t (Higuchi model), and log M t /M ∞ = nlog t+k (Peppas equation). Q t is the amount of drug released at time t and Q 0 is the initial amount of drug present in gels.…”

Section: Mathematical Modeling Of Release Kineticsmentioning

confidence: 99%

Formulation, Characterization, and In Vitro Evaluation of Bioadhesive Gels Containing 5-Fluorouracil

Dhiman

Yedurkar

Sawant

2008

Pharmaceutical Development and Technology

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The objective of this study was to prepare and evaluate in vitro the bioadhesive gels of 5-Fluorouracil (FU) for the treatment of oropharyngeal cancer. In preformulation study, the physicochemical interactions between FU and polymers were investigated by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, and differential scanning calorimetry (DSC). According to FTIR, XRD, and DSC studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. The gel formulations containing FU were prepared by using Poloxamer 407, HPMC K 15 M, and Gantrez ® S-97 (polymethylvinylether-co-maleic anhydride). The formulations contained Poloxamer 407 (16-18% w/w) either alone or in combination with HPMC K 15 M and Gantrez ® S-97. The bioadhesiveness of the gels was found to increase with increasing proportion of HPMC K 15 M and Gantrez ® S-97. In vitro release studies indicated that release could be sustained up to 8 hr. The permeability coefficients (Kp) of gel across cellulose membrane and buccal mucosal membrane were 1.06 × 10 -4 cm/s and 3.94 × 10 -5 cm/s, respectively, and differed significantly ( p < 0.05). Increasing temperature increased the drug release by increasing drug diffusion despite increase in viscosity. The pH of the release medium showed a very slight effect on the release of FU. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as non-Fickian diffusion.

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“…From force-distance plots, the following parameters were derived: (a) compressibility (the work required to deform the product during the compression phase of the probe) was determined as the positive area of the force-distance plot of the compression phase and (b) adhesivity (the work required to overcome the attractive forces between the surface of the sample and the surface of the probe during the decompression phase) was recorded as the negative area of the force-distance plot of the decompression 114 L. C. DU TOIT ET AL. phase, which serves as a good index of the adhesivity of these systems [17].…”

Section: Textural Analysis Of Gel Systemsmentioning

confidence: 99%

Application of Synergism and Variation in Ionic Compatibilities within a Hydrophilic Polymeric Sodium Starch Glycolate-Kappa-Carrageenan Combination: Textural Profiling of the Suspension Behavior

Toit

Pillay

Danckwerts

2006

Journal of Bioactive and Compatible Polymers

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The advantages of starch-carrageenan gel systems have been demonstrated in numerous applications. The exploitation of this functional synergism could provide improvements in the textural properties of a pharmaceutical suspension when prepared employing a combination of the two polymers rather than use of either one alone. This study characterized the influence of kappa-carrageenan (C) on the textural properties of sodium starch glycolate (SSG) through analysis of the textural profiles following forcedisplacement testing. The effect of gel-inducing or gel-strengthening cations on the textural behavior of SSG-C gel systems was also elucidated. The determination of the rate of gelation, as well as the final viscosity of the SSG-C systems was conducted and correlated with the textural properties of the systems. The presence of C in the gel systems significantly increased several textural properties, such as, compressibility (p ϭ 0.002), adhesivity (p ϭ 0.001) and the final viscosity (p ϭ 0.021) of the gels. These properties can be exploited through C's function as a suspending and gelling agent to improve the textural and gel-forming properties of soluble starches, such as, SSG through the establishment of a three-dimensional gel network. Because of the availability of sodium ions in SSG, its combination with C may confer the additional Downloaded from advantage of promoting helix formation and gelation. Neither the presence of gel-inducing nor gel-strengthening cations significantly improved the textural properties of the gel systems (p Ͼ 0.050). The resultant systems, particularly those incorporating the gel-inducing potassium cation, had a heterogenous consistency; they were dense, turbid gels exhibiting water expulsion or syneresis.

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Formulation and Characterisation of Tetracycline-Containing Bioadhesive Polymer Networks Designed for the Treatment of Periodontal Disease

Cited by 20 publications

References 0 publications

Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Formulation, Characterization, and In Vitro Evaluation of Bioadhesive Gels Containing 5-Fluorouracil

Application of Synergism and Variation in Ionic Compatibilities within a Hydrophilic Polymeric Sodium Starch Glycolate-Kappa-Carrageenan Combination: Textural Profiling of the Suspension Behavior

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