Polymeric films for buccal drug delivery

The aim of this research project is to evaluate whether or not pullulan films are suitable to buccal drug delivery of a phosphodiesterase5 (PDE5) inhibitor yonkenafil, which was discovered in our research group and currently is under phase II clinical trial for treatment of erectile dysfunction. Variable formulations of pullulan films were designed and the films were prepared. Mechanical properties of the films, in vitro drug release and polymer dissolution, in vitro drug penetration through porcine esophageal mucosa were investigated. The plasticization effects of solvents, polyols and acids to the films were studied by tensile test, and differential scanning calorimetry, thermogravimetric analysis, fourier transform-infrared, scanning electron microscopy, optical microscopy was applied to analyse the structure and chemical-bonding between pullulan and the additives within the films. Release mathematics models were used in the study of the mechanism of drug releases and polymer dissolutions. Ethanol, menthol, fatty acids, and sodium dodecyl sulphate were employed as penetration enhancers to pretreat the tissue. Various plasticizers and acids were applied into the films and the result showed polyethylene glycol 400 and 600 had the excellent plasticization effect on the drug-free pullulan films, while lactic acid was the best plasticizer for the drug-loaded films. Both PEG400 and lactic acid had a great effect on the drug release from the films in vitro, and all the results indicated that the hydroxyl and carboxyl groups of pullulan and the additives influenced the mechanical properties of the films significantly, and also altered drug release mechanisms. Ethanol shows the greatest enhancing ability on the drug permeation through the porcine esophageal mucosa. A possible mechanism for this is that ethanol interferes with the structure of the lipids in the mucosa, resulting in increased partitioning of the drug into the membrane.

Tactile sensing with fibre Bragg gratings and neural networks

Fibre Bragg grating sensors are usually expensive to interrogate, and part of this thesis describes a low cost interrogation system for a group of such devices which can be indefinitely scaled up for larger numbers of sensors without requiring an increasingly broadband light source. It incorporates inherent temperature correction and also uses fewer photodiodes than the number or sensors it interrogates, using neural networks to interpret the photodiode data. A novel sensing arrangement using an FBG grating encapsulated in a silicone polymer is presented. This sensor is capable of distinguishing between different surface profiles with ridges 0.5 to 1mm deep and 2mm pitch and either triangular, semicircular or square in profile. Early experiments using neural networks to distinguish between these profiles are also presented. The potential applications for tactile sensing systems incorporating fibre Bragg gratings and neural networks are explored.

Design of films for oral dosage formulations

A novel method for tablet coating was studied where a thin polymer film was cast (pre-formed film), dried and applied as a coating hence eliminating the need for using any solvent during the actual coating process. A pre-formed film is initially heating to a temperature where it becomes flexible, a vacuum is applied and the film is then pulled around the tablet. The proposed films (gelatine or cellulose-based) were characterised in terms of their dissolution, swelling, mechanical and thermal properties prior to using them in the novel coating process; selected films were then coated onto tablets containing paracetamol or ibuprofen and the effect of the film on the subsequent dissolution was evaluated. It was found that the pre-formed films could be designed to be fast dissolving and mechanically strong to withstand the stress from the coating process. Also metoclopramide was incorporated in a gelatine film-coating formulation which was then successfully coated on paracetamol-containing core. Gelatin-based films were found to be successful in the novel coating process therefore to be suitable as finished coatings for immediate release dosage forms. Orally disintegrating dosage forms have been identified as a favourable dosage form due to the following reasons: fast onset of drug release, easy to use, not painful and possible increase of amount absorbed to systemic circulation. Selected films formulated for coating studies were also successfully formulated to contain active ingredient suitable for orally disintegrating dosage form; cellulose-based naratriptan-films were studied as orally disintegrating dosage forms of where the effect of formulation on the film properties was studied. It was found that strength of the film can affect the dissolution of the film but it may be the inclusion of specific excipients in the formulation which affect the penetration of the drug through mucosa.

The study of ultra-low energy deposition of hydrogenated amorphous carbon thin films

This thesis is dedicated to the production and analysis of thin hydrogenated amorphous carbon films. A cascaded arc plasma source was used to produce a high density plasma of hydrocarbon radicals that deposited on a substrate at ultra low energies. The work was intended to create a better understanding of the mechanisms responsible for the film formation, by an extensive analysis on the properties of the films in correlation with the conditions used in the plasma cell. Two different precursors were used: methane and acetylene. They revealed a very different picture for the mechanism of film formation and properties. Methane was less successful, and the films formed were soft, with poor adhesion to the substrate and decomposing with time. Acetylene was the better option, and the films formed in this case were harder, with better adhesion to the substrate and stable over time. The plasma parameters could be varied to change the character of films, from polymer-like to diamond-like carbon. Films deposited from methane were grown at low deposition rates, which increased with the increase in process pressure and source power and decreased with the increase in substrate temperature and in hydrogen fraction in the carrier gas. The films had similar hydrogen content, sp3 fractions, average roughness (Ra) and low hardness. Above a deposition temperature of 350°C graphitization occurred - an increase in the sp2 fraction. A deposition mechanism was proposed, based upon the reaction product of the dissociative recombination of CH4+. There were small differences between the chemistries in the plasma at low and high precursor flow rates and low and high substrate temperatures; all experimental conditions led to formation of films that were either polymer-like, soft amorphous hydrogenated carbon or graphitic-like in structure. Films deposited from acetylene were grown at much higher deposition rates on different substrates (silicon, glass and plastics). The film quality increased noticeably with the increase of relative acetylene to argon flow rate, up to a certain value, where saturation occurred. With the increase in substrate temperature and the lowering of the acetylene injection ring position further improvements in film quality were achieved. The deposition process was scaled up to large area (5 x 5 cm) substrates in the later stages of the project. A deposition mechanism was proposed, based upon the reaction products of the dissociative recombination of C2H2 +. There were large differences between the chemistry in the plasma at low and medium/high precursor flow rates. This corresponded to large differences in film properties from low to medium flow rates, when films changed their character from polymer-like to diamond-like, whereas the differences between films deposited at medium and high precursor flow rates were small. Modelling of the film growth on silicon substrates was initiated and it explained the formation of sp2 and sp3 bonds at these very low energies. However, further improvements to the model are needed.

Polymer optical fiber Bragg grating acting as an intrinsic biochemical concentration sensor

We demonstrate an intrinsic biochemical concentration sensor based on a polymer optical fiber Bragg grating. The water content absorbed by the polymer fiber from a surrounding solution depends on the concentration of the solution because of the osmotic effect. The variation of water content in the fiber causes a change in the fiber dimensions and a variation in refractive index and, therefore, a shift in the Bragg wavelength. Saline solutions with concentration from 0% to 22% were used to demonstrate the sensing principle, resulting in a total wavelength shift of 0.9 nm, allowing high-resolution concentration measurements to be realized.

An intrinsic biochemical concentration sensor using a polymer optical fibre Bragg grating

A new type of fibre-optic biochemical concentration sensor based on a polymer optical fibre Bragg grating (POFBG) is proposed. The wavelength of the POFBG varies as a function of analyte concentration. The feasibility of this sensing concept is demonstrated by a saline concentration sensor. When polymer fibre is placed in a water based solution the process of osmosis takes place in this water-fibre system. An osmotic pressure which is proportional to the solution concentration, will apply to the fibre in addition to the hydraulic pressure. It tends to drive the water content out of the fibre and into the surrounding solution. When the surrounding solution concentration increases the osmotic pressure increases to drive the water content out of the fibre, consequently increasing the differential hydraulic pressure and reducing the POFBG wavelength. This process will stop once there is a balance between the osmotic pressure and the differential hydraulic pressure. Similarly when the solution concentration decreases the osmotic pressure decreases, leading to a dominant differential hydraulic pressure which drives the water into the fibre till a new pressure balance is established. Therefore the water content in the polymer fibre - and consequently the POFBG wavelength - depends directly on the solution concentration. A POFBG wavelength change of 0.9 nm was measured for saline concentration varying from 0 to 22%. For a wavelength interrogation system with a resolution of 1 pm, a measurement of solution concentration of 0.03% can be expected.

Discriminating contact in lumen with a moving flexible digit using fibre Bragg grating sensing elements

Minimal access procedures in surgery offer benefits of reduced patient recovery time and less pain, yet for the surgeon the task is more complex, as both tactile and visual perception of the working site is reduced. In this paper, experimental evidence of the performance of a novel sensing system embedded in an actuated flexible digit element is presented. The digit represents a steerable tip element of devices such as endoscopes and laparoscopes. This solution is able to discriminate types of contact and tissue interaction, and to feed back this information with the shape of the flexible digit. As an alternative to this information, force level, force distribution, and other quantifiable descriptors can also be evaluated. These can be used to aid perception in processes such as navigation and investigation of tissues through palpation. The solution is pragmatic, and by virtue of its efficient mechanical construction and a polymer construction, it offers opportunities for a disposable element with suitability for magnetic resonance imaging (MRI) and other scanning environments. By using only four photonics sensing elements, full perception of tissue contact and the shape of the actuated digit can be described in the feedback of this information. The distributive sensory method applied to the sensory signals relies on the coupled values of the sensory data transients of the four deployed sensing elements to discriminate tissue interaction directly in near real time.

Nonlinear response in polymer optical fibre Bragg grating based sensors

PMMA based polymer optical fibre Bragg gratings have been used for humidity, temperature and concentration sensing. Due to the water affinity of PMMA, the characteristic wavelength of the grating is largely modulated by the water content in the fibre. The rate of water transportation between fibre and surrounding depends on the permeability coefficient for PMMA, which is a function of surrounding temperature and humidity. This leads to increased water content with increasing humidity and temperature. Consequently the wavelength of the grating shows a nonlinear change over varying humidity and temperature. This nonlinearity needs to be calibrated prior to sensor application.

Identification of optically clear regions of ternary polymer blends using a novel rapid screening method

The application of a rapid screening method for the construction of ternary phase diagrams is described for the first time, providing detailed visualization of phase boundaries in solvent-mediated blends. Our new approach rapidly identifies ternary blend compositions that afford optically clear materials, useful for applications where transparent films are necessary. The use of 96-well plates and a scanning plate reader has enabled rapid optical characterization to be carried out by transmission spectrophotometry (450 nm), whilst the nature and extent of crystallinity was examined subsequently by wide angle X-ray scattering (WAXS). The moderating effect of cellulose acetate butyrate can be visualized as driving the position of the phase boundaries in poly(l-lactic acid)/polycaprolactone (PLLA/PCL) blends. More surprisingly, the boundaries are critically dependent on the molecular weight of the crystallizable PLLA and PCL, with higher molecular weight polymers leading to blends with reduced phase separation. On the other hand, the propensity to crystallize was more evident in shorter chains. WAXS provides a convenient way of characterizing the contribution of the individual blend components to the crystalline regions across the range of blend compositions. © 2013 Society of Chemical Industry.

Humidity insensitive TOPAS polymer fiber Bragg grating sensor

We report the first experimental demonstration of a humidity insensitive polymer optical fiber Bragg grating (FBG), as well as the first FBG recorded in a TOPAS polymer optical fiber in the important low loss 850nm spectral region. For the demonstration we have fabricated FBGs with resonance wavelength around 850 nm and 1550 nm in single-mode microstructured polymer optical fibers made of TOPAS and the conventional poly (methyl methacrylate) (PMMA). Characterization of the FBGs shows that the TOPAS FBG is more than 50 times less sensitive to humidity than the conventional PMMA FBG in both wavelength regimes. This makes the TOPAS FBG very appealing for sensing applications as it appears to solve the humidity sensitivity problem suffered by the PMMA FBG. © 2011 Optical Society of America.

The accuracy of parameter estimation from noisy data, with application to resonance peak estimation in distributed Brillouin sensing

Distributed Brillouin sensing of strain and temperature works by making spatially resolved measurements of the position of the measurand-dependent extremum of the resonance curve associated with the scattering process in the weakly nonlinear regime. Typically, measurements of backscattered Stokes intensity (the dependent variable) are made at a number of predetermined fixed frequencies covering the design measurand range of the apparatus and combined to yield an estimate of the position of the extremum. The measurand can then be found because its relationship to the position of the extremum is assumed known. We present analytical expressions relating the relative error in the extremum position to experimental errors in the dependent variable. This is done for two cases: (i) a simple non-parametric estimate of the mean based on moments and (ii) the case in which a least squares technique is used to fit a Lorentzian to the data. The question of statistical bias in the estimates is discussed and in the second case we go further and present for the first time a general method by which the probability density function (PDF) of errors in the fitted parameters can be obtained in closed form in terms of the PDFs of the errors in the noisy data.

Investigations on birefringence effects in polymer optical fiber Bragg gratings

Step-index polymer optical fiber Bragg gratings (POFBGs) and microstructured polymer optical fiber Bragg gratings (mPOFBGs) present several attractive features, especially for sensing purposes. In comparison to FBGs written in silica fibers, they are more sensitive to temperature and pressure because of the larger thermo-optic coefficient and smaller Young's modulus of polymer materials. (M)POFBGs are most often photowritten in poly(methylmethacrylate) (PMMA) materials using a continuous-wave 325 nm HeCd laser. For the first time to the best of our knowledge, we study photoinduced birefringence effects in (m)POFBGs. To achieve this, highly reflective gratings were inscribed with the phase mask technique. They were then monitored in transmission with polarized light. For this, (m)POF sections a few cm in length containing the gratings were glued to angled silica fibers. Polarization dependent loss (PDL) and differential group delay (DGD) were computed from the Jones matrix eigenanalysis using an optical vector analyser. Maximum values exceeding several dB and a few picoseconds were obtained for the PDL and DGD, respectively. The response to lateral force was finally investigated. As it induces birefringence in addition to the photo-induced one, an increase of the PDL and DGD values were noticed. © 2014 Copyright SPIE.

Interferometric microstructured polymer optical fiber ultrasound sensor for optoacoustic endoscopic imaging in biomedical applications

We report a characterization of the acoustic sensitivity of microstructured polymer optical fiber interferometric sensors at ultrasonic frequencies from 100kHz to 10MHz. The use of wide-band ultrasonic fiber optic sensors in biomedical ultrasonic and optoacoustic applications is an open alternative to conventional piezoelectric transducers. These kind of sensors, made of biocompatible polymers, are good candidates for the sensing element in an optoacoustic endoscope because of its high sensitivity, its shape and its non-brittle and non-electric nature. The acoustic sensitivity of the intrinsic fiber optic interferometric sensors depends strongly of the material which is composed of. In this work we compare experimentally the intrinsic ultrasonic sensitivities of a PMMA mPOF with other three optical fibers: a singlemode silica optical fiber, a single-mode polymer optical fiber and a multimode graded-index perfluorinated polymer optical fiber. © 2014 SPIE.

Inscription of narrow bandwidth bragg gratings in polymer optical fibers

We report on the production and characterization of narrow bandwidth fiber Bragg gratings (FBGs) in two spectral regions using polymer optical fibers (POFs). Narrow bandwidth FBGs are increasingly important for POF transmission systems, WDM technology and sensing applications. Long FBGs with resonance wavelength around 850 nm and 1550 nm were fabricated in several types of polymer optical fibers. The 3 dB FBG bandwidth varies from 0.22 nm down to 0.045 nm considering a Bragg grating length of 10 mm and 25 mm, respectively. © 2013 SPIE.