Bioadhesive System Research Articles

Prospective and New Findings of Hydroxypropyl Methylcellulose (HPMC) as a Potential Carrier for Gastrorententive Drug Delivery Systems

Gastroretentive drug delivery systems are able to prolong the overall gastric residence time and can improve the oral bioavailability of the medicaments that show site specific absorption from the stomach or upper part of the small intestine. Various approaches are currently utilized to retain the dosage form in the stomach including polymeric bioadhesive systems, floating drug delivery systems, swelling and expanding systems, high density systems, biodegradable hydrogel systems and other delayed gastric emptying devices. Among the numerous polymers that are being used for gastroretentive drug delivery systems, hydroxylpropyl methyl cellulose (HPMC), possessing hydrophilic and gel forming properties, is extremely advantageous. It is also nontoxic and biocompatible. In this article, the important properties of HPMC and various techniques used for preparing gastroretentive dosage forms based on HPMC are reviewed. This review also includes the investigation of various classes of drugs used for preparing HPMC based gastroretentive drug delivery system. Keywords: Hydroxypropylmethylcellulose, Floating gastroretentive tablets, Controlled release, Bioadhesion, Capsules, Pellets.

Alternative Chitosan Based Drug Delivery System to Fight Oral Mucositis: Synergy of Conventional and Bioactives Towards the Optimal Solution

Chitosan based novel occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis based on chitosan, suitable surfactants (Cetyl trimethylammonium bromide and Polyquaternium-1 (Polyquad®)) and Propolis ethanolic extract were developed and evaluated in this investigation. The positive synergy was observed combined the antifungal and antioxidant capacity of synthetic and natural biomaterials into functional biocompatible gel. The in vitro antioxidant capacity (free radical scavenging by ORAC and intrinsic reducing capacity by Folin-Ciocalteu Method) was quantified and the influence of antioxidant capacity of Propolis extract on the rate of release of nystatin, from chitosan based material was investigated. These copolymer systems are able to release the drug over several weeks and therefore may be useful as a drug carrier in the treatment of oral mucosatis. Keywords: Antiooxidants, chitosan, hydrogels, oral mucosatis, free radicals, functional materials

Floating and bioadhesive delivery system of metoprolol succinate: Formulation, development and in vitro evaluation

Floating and bioadhesive delivery system of metoprolol succinate: Formulation, development and in vitro evaluation

Letter to the Editor [Buccoadhesive Dosage Form Containing Antifungal Agent for Treating Oropharyngeal Candidiasis: A Review (One More Buccoadhesive Antifungal for Oropharyngeal Candidiasis)

Dear Editor, In the above mentioned review article, a comprehensive list of active ingredients investigated in bioadhesive dosage forms for the treatment of OPC was presented, various kind of active agents and dosage forms have been mentioned but one agent Miconazole base is omitted. The active ingredients are •Miconazole 50 mg buccal tablet (MBT) (Oravig™, Strativa Pharmaceuticals). •Miconazole nitrate 10 mg buccal tablets (Tibozole™, Tibotec Pharmaceuticals) The above mentioned buccal tablets were used in the treatment for OPC. However, the two miconazole buccal tablets are distinct products, and each contains different polymers. MBT utilizes a hydrophilic matrix containing the polymer hypermellose, which allows immediate and sustained release of Miconazole [1]. Advantages Over Conventional Dosage Forms •Once daily dosing lacking in nystatin oral suspension and clotrimazole troches, which are dosed 4 to 5 times daily. •Good bioadhesion (hypermellose mucoadhesive polymer) •Minimal systemic drug exposure •Controlled drug release pattern Following single-dose application of MBT, the plasma concentrations of miconazole were below the lower limit of assay quantification (0.4 mcg/mL) in 97% of samples (157/162) from 18 healthy volunteers [2,3]. In those plasma samples with measurable miconazole levels, concentrations did not exceed 0.83 mcg/mL. Currently in the United States, MBT is the only miconazole buccal tablet available. REFERENCES [1] Aiache JM, Costantini D, Chaumont C, inventors; BioAlliance Pharma, assignee. Sustained-release therapeutic bioadhesive systems. Patent WO/2003/009800. June 2, 2003. [2] Cardot JM, Chaumont C, Dubray C, et al. Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects. Br J Clin Pharmacol 2004; 58(4): 345-51. [3] Oravig [prescribing information]. Woodcliff Lake, NJ: Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc.; April 2010.

Letter to the Editor [Response to: Buccoadhesive Dosage Form Containing Antifungal Agent for Treating Oropharyngeal Candidiasis: A Review(One More Buccoadhesive Antifungal for Oropharyngeal Candidiasis)

Dear Editor, The review of buccoadhesive drug delivery systems and their logical use for the local treatment of oropharyngeal candidiasis (OPC) by Pendekal, Shariff, and Tegginamat [1] is a useful reference describing the use of buccoadhesive dosage forms for drug delivery. Although a comprehensive list of active ingredients investigated in bioadhesive dosage forms for the treatment of OPC was presented, one agent omitted was miconazole base. This active ingredient is commercially available as miconazole 50 mg buccal tablet (MBT) (Oravig™, Strativa Pharmaceuticals). Miconazole nitrate 10 mg buccal tablets (Tibozole™, Tibotec Pharmaceuticals) was noted as a treatment for OPC, however, the two miconazole buccal tablets are distinct products, and each contains different polymers. MBT utilizes a hydrophilic matrix containing the polymer hypermellose [2], which allows immediate and sustained release of miconazole during the day [3]. As the authors indicated, the controlled release of antifungal medication when treating OPC is beneficial to provide prolonged local treatment of the fungal infection. Hypermellose also confers mucoadhesive properties. Among the desired characteristics listed by the authors for buccoadhesive treatments for OPC, convenient dosing should be included since the controlled release drug delivery facilitates once-daily dosing. Both MBT and miconazole nitrate buccal tablets are dosed once-daily, which is in contrast to other local treatments for OPC, such as nystatin oral suspension and clotrimazole troches, that are dosed 4 to 5 times daily. An OPC infection is local to the mouth and throat, and a benefit of treating OPC locally with MBT is minimal systemic drug exposure [3]. Following single-dose application of MBT, the plasma concentrations of miconazole were below the lower limit of assay quantification (0.4 mcg/mL) in 97% of samples (157/162) from 18 healthy volunteers [3,4]. In those plasma samples with measurable miconazole levels, concentrations did not exceed 0.83 mcg/mL. Currently in the United States, MBT is the only miconazole buccal tablet available; miconazole nitrate 10 mg buccal tablet is not commercially available in the United States. AUTHOR DISCLOSURE AND CONFLICT OF INTEREST Dr. Naomi Musaji is an employee of Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc. There are no other affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. REFERENCES [1] Pendekal MS, Shariff M, Tegginamat PK. Buccoadhesive dosage form containing antifungal agent for treating oropharyngeal candidiasis: A review. Current Drug Therapy 2011; 6: 55-64. [2] Aiache JM, Costantini D, Chaumont C, inventors; BioAlliance Pharma, assignee. Sustained-release therapeutic bioadhesive systems. Patent WO/2003/009800. June 2, 2003. [3] Cardot JM, Chaumont C, Dubray C, et al. Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects. Br J Clin Pharmacol 2004; 58(4): 345-51. [4] Oravig [prescribing information]. Woodcliff Lake, NJ: Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc.; April 2010. Keywords: Buccal tablet, buccoadhesive, candidiasis, hypermellose, miconazole

BILAYER AND FLOATING-BIOADHESIVE TABLETS: INNOVATIVE APPROACH TO GASTRORETENSION

A bilayer and floating-bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong residence in the stomach. Bilayer tablet is new era for the successful development of controlled release formulation along with various features to provide a way of successful drug delivery system. Controlled release (CR) dosage forms have been extensively used to improve therapy with several important drugs. Incorporation of the drug in a controlled release gastroretentive dosage forms (CR-GRDF) which can remain in the gastric region for several hours would significantly prolong the gastric residence time of drugs and improve bioavailability, reduce drug waste, and enhance the solubility of drugs that are less soluble in high pH environment. Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), swelling and expanding systems, polymeric bioadhesive systems, high-density systems, modified-shape systems and other delayed gastric emptying devices. The floating and bioadhesive drug delivery systems are considerably easy and logical approach. An attempt has been made in this review article to introduce the society to the current technological developments in bilayer and floating- bioadhesive drug delivery system

Preparation and characterization of bioadhesive systems containing propolis or sildenafil for dental pulp protection

Purpose: Binary polymeric systems containing poloxamer 407 (P407) and Carbopol 934P (C934P) were designed to deliver propolis extract (PE) or sildenafil citrate for the endodontic treatment (pulp protection).Methods: Gelation temperature, rheology (flow), bioadhesion, and in vitro drug release of formulations were determined.Results: Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34–37°C. In addition, they exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. The greatest bioadhesion was noted in the formulation containing 20% P407 (w/w) and 0.10% C934P (w/w). PE release from formulation containing 15% P407 (w/w) and 0.25% C934P (w/w) was controlled by the phenomenon of relaxation of polymer chains. Moreover, sildenafil release from formulation containing 20% P407 (w/w) and 0.10% C934P (w/w) was controlled by Fickian diffusion.Conclusion: The data obtained on these formulations indicate a potentially useful role in the endodontic treatment (pulp protection) and suggest they are worthy of clinical evaluation.

Gecko‐Inspired Dry Adhesive for Robotic Applications

AbstractMost geckos can rapidly attach and detach from almost any kind of surface. This ability is attributed to the hierarchical structure of their feet (involving toe pads, setal arrays, and spatulae), and how they are moved (articulated) to generate strong adhesion and friction forces on gripping that rapidly relax on releasing. Inspired by the gecko's bioadhesive system, various structured surfaces have been fabricated suitable for robotic applications. In this study, x–y–z asymmetric, micrometer‐sized rectangular flaps composed of polydimethylsiloxane (PDMS) were fabricated using massively parallel micro‐electromechanical systems (MEMS) techniques with the intention of creating directionally responsive, high‐to‐low frictional‐adhesion toe pads exhibiting properties similar to those found in geckos. Using a surface forces apparatus (SFA), the friction and adhesion forces of both vertical (symmetric) and angled/tilted (x–y–z asymmetric) microflaps under various loading, unloading and shearing conditIons were investigated. It was found that the anisotropic structure of tilted microflaps gives very different adhesion and tribological forces when articulated along different x–y–z directions: high friction and adhesion forces when articulated in the y–z plane along the tilt (+y) direction, which is also the direction of motion, and weak friction and adhesion forces when articulated against the tilt (–y) direction. These results demonstrate that asymmetric angled structures, as occur in geckos, are required to enable the gecko to optimize the requirements of high friction and adhesion on gripping, and low frictional‐adhesion on releasing. These properties are intimately coupled to a (also optimum) articulation mechanism. We discuss how both of these features can be simultaneously optimized in the design of robotic systems that can mimic the gecko adhesive system.

Polysaccharide-Based Adhesive for Biomedical Applications: Correlation between Rheological Behavior and Adhesion

Adhesion to biological tissues is a challenge especially when the adhesive is in contact with physiological fluids. Abdominal hernia is a disease that often requires the implantation of a mesh within the abdominal wall. To minimize pain and postsurgical complications, gluing the mesh appears to be a convenient method. For this purpose, a bioadhesive system based on solutions of chitosan and modified starch (oxidized maltodextrin) has been developed. Mixtures of these polysaccharides form either viscoelastic solutions or hydrogels, depending on various experimental parameters (chitosan concentration, starch degree of oxidation, molar ratio between amine and aldehyde functions, pH, etc.). An adhesion test was developed to assess the adherence of such systems under conditions similar to the intended use. The rheological behavior of each formulation was correlated to its adherence, and it was found that optimum adhesion is obtained for systems exhibiting an intermediate behavior between the viscoelastic solution and the gel.

Drug Delivery: Plant Lectins as Bioadhesive Drug Delivery Systems

Selective targeting of drugs to the proposed site of action provides therapeutic advantages such as reduced toxicity and smaller dose levels. Despite a huge progress made in drug design and delivery systems, many challenges still have to be solved. Small therapeutic drugs always have the potential to pass into the kidneys and be excreted from the body. The use of macromolecular constructs (carriers) that allow longer circulation times, contribute to improved chemical functionality and more precise drug delivery is an attractive alternative option. Bioadhesive systems which will utilize intense contact to increase the drug concentration gradient could be an attractive approach. Because of their specific carbohydrate-binding, lectins can interact with glycoconjugates present on the epithelial cells that line all of the organs exposed to the external environment. The unique carbohydrate specificities of plant lectins can facilitate mucoadhesion and cytoadhesion of drugs. As immunostimulatory molecules with an adjuvant effect plant lectins can also be employed in vaccine development.

Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers on the Release Rate and In Vitro Evaluation

Extending the residence time of a dosage form at a particular site and controlling the release of drug from the dosage form are useful especially for achieving controlled plasma level of the drug as well as improving bioavailability. The objective of this study was to extend the GI residence time of the dosage form and control the release of Tramadol HCl using mucoadhesive tablet to achieve controlled plasma level of the drug which is especially useful for 12 hrs. Matrix tablets of Tramadol HCl were formulated using different mucoadhesive polymers namely guar gum, xanthan gum and Methocel (HPMC K15M and HPMC K100M). Formulations were evaluated for preformulation parameters, in vitro drug release profile and release kinetics. The formulations were found to have good preformulation characteristics. FTIR spectroscopy indicated the absence of any significant chemical interaction within dug and excipients. The release mechanism of Tramadol HCl from matrix tablets indicated anomalous (non-Fickian) transport mechanism and followed zero order kinetics. The retention time of the mucoadhesive tablet on the mucous membrane were investigated to develop a bioadhesive polymer-based controlled release delivery system and to evaluate the performance of such a delivery devices. The combination of HPMC K15: HPMC K100: Xanthan gum (1:2:1) and HPMC K 100: Xanthan gum (2:2) showed a greater bioadhesive strength as compared to single gum and other hydrophilic polymer combination tablet. The stability studies were performed on optimized formulation as per ICH guideline, result showed that there was no significant change in physical characteristic, adhesive strength and In vitro release.

Novel patch-based systems for the localised delivery of ALA-esters

In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 μmol cm −2) were associated with significantly greater tissue concentrations (70.7 μmol cm −3) than patches containing m-ALA (16.3 μmol cm −3) or h-ALA (17.4 μmol cm −3). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 a.u., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced.

Characterisation of a new bioadhesive system based on polysaccharides with the potential to be used as bone glue

Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff's base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.

A Novel Intravaginal Delivery System for Itraconazole: In Vitro and In Vivo Evaluation

The purpose of the present study was to formulate and systematically evaluate in vitro, ex vivo and in vivo performances of itraconazole containing bioadhesive vaginal film. We introduce here a novel intravaginal delivery system for itraconazole based on solid dispersion of itraconazole and hydroxypropyl methylcellulose E15 that improve drug solubility and produce bioadhesive system in presence of other ingredients. Solid dispersions of itraconazole were prepared with hydroxypropyl methylcellulose by a spray drying method and characterized by X-ray diffraction and differential scanning calorimetry. The film was prepared using a solvent evaporation technique. In the in vitro antimicrobial study, it was found that solid dispersion containing formulation improves antimicrobial action of itraconazole. From the ex vivo retention study, it was found that the bioadhesive polymers hold the film upto 7 hours on the vaginal mucosa. In vivo antifungal activity tested against Candida albicans vaginitis in female rats, was found to significantly improve the therapeutic benefit of the drug. At 6 days post-dose, the c.f.u. of Candida albicans was more than 10(3) fold decreased in film treated groups without affecting the morphology of vaginal mucosa. These studies suggested that bioadhesive vaginal film is a novel approach for delivery of itraconazole as topical drug delivery system for treating vaginal candidiasis.

Periodontal Muco-Adhesive Formulations for the Treatment of Infectious Periodontal Diseases

Extensive efforts have recently been focused on targeting a drug or delivery system in a particular region of the body for extended period of time, not only for local targeting of drugs but also for the better control of systemic drug delivery. The concept of periodontal drug delivery systems has fascinated many investigators to the possible use of various polymers, which can overcome various physiological barriers in long-term drug delivery, there by rendering the treatment more effective and safe for local disorders and systemic problems. Presence of a smooth and relatively immobile surface for placement of a bio-adhesive dosage form has made periodontal route more suitable for sustained delivery of therapeutic agents using bio-adhesive systems. Antibiotics, antiseptics and other poorly absorbable drugs can be successfully delivered via periodontium for the treatment of infectious periodontal diseases. The dosage forms include microparticles, microspheres, adhesive gels, adhesive films, adhesive creams and ointments. Bio-adhesive periodontal drug delivery system can also exert positive influence on drug effectiveness by keeping the drug in the region proximal to its absorption window and allow the targeting and localization of the drug at the specific site.

The cumulative effect of urea 40% combined with essential fatty acids in a bioadhesive delivery system and ketoconazole cream 2% for the treatment of moccasin tinea pedis in diabetics

The cumulative effect of urea 40% combined with essential fatty acids in a bioadhesive delivery system and ketoconazole cream 2% for the treatment of moccasin tinea pedis in diabetics

A Novel Multicompartment Dissolution Apparatus for Evaluation of Floating Dosage Form Containing Poorly Soluble Weakly Basic Drug

Introduction Oral controlled release (CR) dosage forms generally have a transit time of 1–3 hours in the stomach,3–5 hours in the intestine and 4–11 hours in the colon(1). However,some drugs require more retention time in the stomach for better results. Gastro-retentive drug delivery is superior for drugs such as (a) drugs having a narrow absorption window,(b) drugs having their local effect in stomach (for example,antacids and anti helicobacter pylori agents), (c) drugs having pH-dependent stability, (d) drugs having low solubility at intestinal pH,and (e) drugs having colonic degradation (2,3). Approaches to achieve higher gastric residence time include (a) low density systems that float on gastric fluid, (b) bioadhesive systems that adhere to mucosal surface of stomach,(c) expandable systems that increase in size by swelling or unfolding to retard passage through the pylorus, (d) high density systems that sink in the lower curvature of the stomach,(e) magnetically controlled systems that operate by incorporation of magnetite oxide or coated magnets (4–6). Weakly basic drugs have lower pKa values and remain in ionized form at stomach pH having higher solubility,and in un-ionized form at intestinal pH having lower solubility (7). According to pH partition theory (14),drug is absorbed in un-ionized form,thus weakly basic drug absorbs from the intestine. When weakly basic drug is incorporated in a conventional CR dosage form,only a fraction of the drug is dissolved due to lesser solubility at its absorption site,such as the intestine. Incorporation of weakly basic drug into a gastro-retentive dosage form is beneficial over a conventional CR dosage form so that released drug continuously reaches its absorption site such as the intestine (8). Cinnarizine is a weak base (pKa 1.95,7.5) having higher solubility at lower pH (0.29 mg/mL in 0.1 N HCl) and lower solubility at higher pH (0.002 mg/mL in phosphate buffer pH 7.2),and thus is selected as the model drug for the floating dosage form (9,10). In vitro dissolution testing is generally carried out for quality control purposes and to establish an in vivo in vitro correlation. The currently used in vitro dissolution method for the floating dosage form is conducted at a constant pH 1.2 to mimic the stomach environment. The general prediction is that when drug is dissolved in vitro, it is considered that the drug is also absorbed in vivo. However, in vivo,the drug is exposed to varying dissolution environments in the gastrointestinal (GI) tract. Particularly,the pH in the GI tract Abstract Incorporation of a weakly basic drug into a gastro-retentive dosage form yields better biomedical benefits compared to incorporation into a conventional controlled release dosage form. Poorly soluble weakly basic drugs may precipitate upon entry into the small intestine,and this can affect absorption. To study drug release from floating dosage forms and simultaneously examine the effect of pH change on poorly soluble weakly basic drugs,a novel multicompartment dissolution system was developed by modifying beakers. The system consists of three serially placed compartments providing gastric, intestinal, and absorption compartment to mimic the in vivo dissolution and absorption in the gastrointestinal tract. A dosage form remained buoyant in the gastric compartment,released drug was allowed to transfer to the intestinal compartment,and soluble drug in the intestinal compartment was allowed to transfer to the absorption compartment through a filter. Dissolution profiles of 75 mg cinnarizine in conventional and floating tablets were studied. The results of conventional tablet showed that although cinnarizine was completely dissolved in the gastric compartment,approximately 50% of cinnarizine was precipitated in the intestinal compartment. A floating cinnarizine tablet showed complete release within 24 hours with nearly zero order release rate,and no precipitation observed in the intestinal compartment,giving 100% of cinnarizine transferred into the absorption compartment. The floating controlled release of poorly soluble weakly basic drug may give considerable biomedical benefits over conventional tablet formulation,which was demonstrated by the proposed novel multicompartment system. Variability of volume in the gastric and intestinal compartments was studied by making further modification in the apparatus. The proposed system may give good in vivo in vitro correlation,as attempts can be made to mimic in vivo conditions such as gastric volume,gastric secretion,gastric emptying to the intestine,and intestinal absorption.

Pharmaceutical analysis of 5-aminolevulinic acid in solution and in tissues

Quantification of 5-aminolevulinic acid (ALA) in solution, and methods used to achieve this, have been extensively reported in the literature. However, validated methods have only rarely been presented and never have methods been compared. Due to a necessity in drug delivery research for optimised and validated methods for determination of ALA in solution, this paper compares, for the first time, two such methods validated to International Conference on Harmonisation (ICH) standards. Of major importance, derivatisation of ALA with acetyl acetone and formaldehyde was found to be more suitable for routine fluorimetric HPLC analysis of ALA than derivatisation with o-phthaldialdehyde and 2-mercaptoethanol. This former method was successfully utilised in the comparison of in vitro drug release from a proprietary ALA cream and a novel bioadhesive patch-based system. In addition, determination of ALA in tissue is necessary to compare different topical formulations, in terms of their ability to deliver the drug successfully, and different tissue types, to assess their barrier properties to penetration of the drug. Consequently, this paper also describes the use of liquid scintillation spectroscopy as an analytical tool for rapid, convenient and routine quantification of ALA in tissue and determination of penetration depth following topical application of creams and patches.

Drug Delivery Strategies for the Treatment of Helicobacter pylori Infections

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated.

Optimizing Drug Delivery Systems Using Systematic "Design of Experiments." Part II: Retrospect and Prospects

The first study on application of Design of Experiments (DoE) in optimizing drug formulation appeared in 1967. Since then the number of literature reports on the use of DoE optimization in development of drug delivery technologies has been piling up steadily. Such systematic techniques find their use in every type of conventional dosage form and modern drug delivery system. The drug delivery devices investigated for optimization using response surface methodology include controlled release compressed matrices, microparticulates, macroparticulates, vesicular systems, floating systems, bioadhesive systems, semisolids, transdermals, and inhalations. The optimized processes mainly include extrusion-spheronization, pelletization, microencapsulation, coating, granulation, and tableting. Part I of this article [Crit Rev Ther Drug Carrier Syst 2005; 22(1):27-106] dealt with the salient steps involved in the DoE optimization methodology using diverse experimental designs. Part II deals with various retrospective literature findings as well as the prospective application of such DoE procedures while optimizing varied drug delivery technologies. A vast account of various DoE reports on optimization of diverse drug delivery system and processes along with the critical graphical analysis of various designs, input, and response variables have been presented here in a categorical form. Such an explicit and updated review on drug delivery optimization has not been published anywhere else in the recent past.