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Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD). Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release. Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved. Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area. [ABSTRACT FROM AUTHOR]

Periodontal disease is a chronic inflammation of gum and tissues that surround and support the teeth. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in the treatment of periodontitis to ease swelling and inflammation. One approach of treating periodontitis is loading the NSAIDs in local drug delivery systems. Therefore, the objective of this study was to investigate the local delivery of the NSAIDs model drug ibuprofen to treat periodontitis using different types of gel formulations (hydrogel, oleogel, and bigel). Gel formulations were characterized in terms of their rheological properties (flow behavior, viscoelastic, and bioadhesive properties) using a controlled-stress rheometer. The in vitro drug release of ibuprofen from gel formulations was investigated using Franz diffusion cells. Gels exhibited more solid-like (elastic) behavior. The viscosity and viscoelastic properties were in the order of oleogel > bigel > hydrogel, respectively. In bioadhesion study, mucin dispersion/plain ibuprofen-hydrogel mixture showed a frequency-dependent interaction of ΔG’ = −31 and ΔG’ = + 53 Pa at 1 and 10 rad/s, respectively. A strong positive interaction (ΔG’ = + 6000 and +130,667 Pa at 1 and 10 rad/s, respectively) was found in mucin dispersion/plain ibuprofen-oleogel mixture. The extent of the negative interaction increased in mucin dispersion/plain ibuprofen-bigel mixture (ΔG’ = −59,000 and −79,375 Pa at 1 and 10 rad/s, respectively). After 6 h, ibuprofen release from hydrogel, oleogel, and bigel was 59.5 ± 2.2, 80.6 ± 3.9, and 94.6 ± 3.2%, respectively. Results showed that the rheological and bioadhesive properties and in vitro drug release were influenced by the type of gel formulations. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate and compare four different thiolated polymers regarding their dermoadhesive potential. Therefore, three hydrophilic polymers (poly(acrylic acid), Carbopol 971 and carboxymethylcellulose) and a lipophilic polymer (silicone oil) were chosen to generate thiolated polymers followed by characterization. The total work of adhesion (TWA) and the maximum detachment force (MDF) of formulations containing modified and unmodified polymers were investigated on skin obtained from pig ears using a tensile sandwich technique. The synthesis of thiolated polymers provided 564 µmol, 1079 µmol, 482 µmol and 217 µmol thiol groups per gram poly(acrylic acid), Carbopol 971, carboxymethylcellulose and silicone oil, respectively. Hydrogels containing poly(acrylic acid)-cysteine, Carbopol 971-cysteine, and carboxymethylcellulose-cysteamine exhibited a 6-fold, 25-fold and 9-fold prolonged adhesion on porcine skin than the hydrogel formulations prepared from the corresponding unmodified polymers, respectively. Furthermore, thiolation of silicone oil with thioglycolic acid led to a 5-fold improvement in adhesion compared to the unmodified silicone oil. A comparison between the four thiolated polymer formulations showed a clear correlation between the amount of coupled thiol groups and the TWA. According to these results thiomers might also be useful excipients to provide a prolonged dermal resistance time of various formulations. [ABSTRACT FROM PUBLISHER]

This study describes the investigation about the physicochemical behavior of methylene blue (Mb) addition to systems containing poloxamer 407 (Polox), Carbopol 934P (Carb), intended to be locally used by photodynamic therapy. A factorial design 23(plus center point) was used to analyze the rheological, mucoadhesive and textural properties of the preparations. Systems containing the lower concentrations of Polox (15 and 17.5%, w/w) exhibited pseudoplastic flow and low degrees of rheopexy. On the other hand, at higher Polox concentration (20%, w/w) the systems display plastic flow and thixotropy. Carb and Mb exhibited a negative influence for the consistency and flow behavior index, due to the interaction between them. For most of the formulations, the increase of Polox and Mb content significantly increased storage modulus, loss modulus and dynamic viscosity. The systems display a sol–gel transition temperature, existing as a liquid at room temperature and gel at 29–37 °C. Increasing the temperature and the polymer concentration, the compressional properties of systems significantly increased. The mucoadhesion was noted to all formulations, except to systems composed by 15% (w/w) of Polox. The analyses enabled to understand and predict the performance of formulations and the polymer–Mb interactions, tailoring to the suit systems (Polox/Carb/Mb): 17.5/0.50/0.20 and 20/0.15/0.25. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present investigation was the development andin vivocharacterization of domperidone (DOM) hot-melt extruded (HME) controlled release films by central composite design (CCD) for buccal delivery. Methods: Concentration of PEO N750 (X1) and HPMC E5 LV (X2) as independent variables and tensile strength (Y1), percent drug release at 6 h (Q6,Y2) and percent drug permeated at 6 h (Y3, P6) as responses. In total, 13 formulations were prepared and studied. HME films were evaluated for drug excipient compatibility, physico-mechanical properties, drug content,in vitrodrug release, bioadhesion, swelling and erosion,ex vivopermeation. Furthermore, statistically optimized formulation was subjected for bioavailability studies in healthy human volunteers. Results: Statistically optimized formulation exhibited a tensile strength (3.86 kg/mm2), 93.62 ± 2.84% of drug release and 63.36 ± 2.12% of drug permeated in 6 h. HME films demonstrated no drug excipient interaction and excellent content uniformity. Furthermore, optimized formulation exhibited elongation at break (38.6% mm2), peak detachment force (1.75 N), work of adhesion (3.21 mJ), swelling index (240.4%) and erosion (8.5%). Bioavailability from the statistically optimized buccal films was 3.2 times higher than the oral dosage form (p < 0.05). Theex vivo–in vivocorrelation was found to have biphasic pattern and followed type A correlation. The stability of the optimized formulation was studied and no significant changes were detected in 6 months. Conclusion: The results indicate that hot-melt extrusion is a viable technique for the preparation of DOM buccal-adhesive controlled release films with improved bioavailability by CCD. [ABSTRACT FROM AUTHOR]

The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too. [ABSTRACT FROM AUTHOR]

Background: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems. Aim: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin. Methods: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels. Results: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin. Conclusion: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin. [ABSTRACT FROM AUTHOR]

The objective was to investigate the potential of polymer molecular weight (MW) and polymer blends for the control of drug release from in situ gelling nasal inserts prepared by lyophilization of solutions of model drugs (oxymetazoline HCl, diprophyllin) and polymers. Drug release, polymer solution viscosity, water uptake and mass loss, mechanical properties, and bioadhesion potential were measured. Sonication was effective to reduce the viscosity/polymer MW of carrageenan solutions. Nasal inserts prepared from sonicated carrageenan showed an insignificant reduction in water uptake with sonication time and no disintegration of the gel matrix. In contrast, inserts of different MW Na-alginates revealed a reduced water uptake and an increased mass loss with lower MW. Inserts prepared from carrageenan/low MW Na-alginate blends took up more water at a higher low MW Na-alginate content. Sonicated carrageenan inserts released oxymetazoline HCl independent of the sonication time and diprophyllin with only a slight reduction in the release rate. Release of both drugs from Na-alginate inserts was slow from high MW inserts because no insert dissolution occurred. Increasing the Na-alginate content of inserts prepared from polymer blends accelerated the drug release enabling release rates over a broad range. The bioadhesion potential of Na-alginate inserts was strongly reduced for the low MW grades because of dissolution of the inserts. Xanthan gum and Carbopol 971 blended with Na-alginate formed inserts with poor bioadhesion. The use of polymer blends to control the drug release from nasal inserts was superior to the use of polymers of different MW. [ABSTRACT FROM AUTHOR]

Context: Treatment of chronic pain is complicated by the evidence that abuse of prescription opioids is rising; therefore, in many cases, chronic pain remains undertreated. Tramadol is an atypical central analgesic with a mixed mechanism of action offering many advantages over conventional opioids. Objective: We exploited the nonopioid action of tramadol, by bypassing the first-pass effect, as well as multiparticulate drug delivery. Our aim was to identify optimal formulation parameters for designing polyvinyl alcohol (PVA), single and mixed dual cross-linked tramadol microspheres-loaded hydrogel with adequate bioadhesion and providing controlled drug release for buccal delivery. Methods: Microspheres characterization was done by scanning electron microscopy and infrared spectroscopy. Other investigations comprised the evaluation of yield, drug content, particle size, rheology, swelling, mucoadhesion, release, and permeation studies through biological membranes all together with testing the antinociceptive activity and its attenuation by the antagonist naloxone HCl. Results and conclusion: PVA-alginate microspheres (F3)-loaded carbopol hydrogel attained: the highest mucoadhesion time (1436.67 min ± 5.77) and mucin adsorption capacity, shear thinning thixotropic properties with adequate yield value and hysteresis area, best drug release (RE == 84.20 ± 2.07%) and permeation efficiency (PE == 65.30 ± 7.02%). Dissolution and permeation profiles were compared using similarity factor; F3-loaded carbogel had the lowest value. During in vivo study, the nonsignificant difference between the AUC of the groups receiving F3-loaded carbogel buccally with (group 5) and without (group 4) administration of naloxone, and between group 4 and the oral group, showed that the buccal route may arguably provide an alternative safer route of tramadol administration. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the muco//bioadhesive properties of chitosan, polyvinylpyrrolidone (PVP), and chitosan//PVP blends and the release of amoxicillin (AMX) contained in AMX-alginate beads coated with these materials. Method: Chitosan, PVP, and chitosan//PVP blends at various volume ratios were coated onto calcium alginate beads containing AMX. The muco//bioadhesive properties of all materials and the AMX-alginate beads coated with these materials were characterized. Results: Measurements of their viscosity, texture, and adhesion to HT29 cells demonstrated that chitosan//PVP at a volume ratio of 5//5 had the best muco//bioadhesive properties when compared with chitosan, PVP, and blends of other ratios. Wash-off tests indicated that the mucoadhesive property of the coated AMX-alginate beads was significantly higher than that of the uncoated beads. Diffuse reflectance infrared Fourier transform spectroscopy showed that there were interactions between chitosan--PVP, chitosan--mucin, PVP--mucin, and chitosan//PVP blend--mucin. Scanning electron microscopy revealed that the surfaces of the coated beads were smoother than those of the uncoated beads. All coated AMX-alginate beads were able to provide a controlled release of AMX with Super Case II transport properties, at a pH of 4. This was probably a result of the rapid and extensive swelling of the alginate beads. The more rapid release of AMX at pH 1 was probably because of the rapid dissolution of the drug at this pH. Conclusions: From the controlled drug release and muco//bioahesive properties of these coated AMX-alginate beads, we suggest that the alginate-coated beads might be a promising drug delivery system to assist with the eradication of Helicobacter pylori infections. [ABSTRACT FROM AUTHOR]

Background: Poly (ethylene oxide) (PEO) is nonionic, water soluble, and highly hydrophilic polymer with well-established applications in mucoadhesives, water-soluble films, rheology control agents and thickeners, and additives in pharmaceutical products. Methods: Different powder blends containing PEO in varying proportions were evaluated for their flow, compressive, and bioadhesive properties and subsequently compressed into gastroretentive tablets. Two optimized formulations, on the basis of above-mentioned examinations, were subjected to gamma scintigraphy studies on human volunteers. Results: The values of bulk and tapped densities, Hausner ratio and Carr index, angle of repose, loss on drying, total moisture content, and particle size distribution provided a fine estimation of flowability and compressibility of the powder blends. Further, apart from the routine pharmacopoeial assessments, the evaluation of compressed tablets for their surface pH in both acidic and basic environments nullified the possibility of any irritation to the membrane where it is intended to adhere. The measurement of swelling index and bioadhesive strength of tablets revealed that both the parameters were a direct function of the concentration of PEO in the tablet. The results of gamma scintigraphy indicated a fourfold increase in the gastric retention time of the optimized formulation vis-à-vis control formulation. Conclusion: The results indicate that PEO, in a concentration of 10–50% (w/w), can be successfully employed in manufacturing gastroretentive tablets. [ABSTRACT FROM AUTHOR]

Background: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. Aim: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. Method: Interaction between atenolol and randomly methylated β-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. Results: The formation of a stabile inclusion complex ( Ks = 783.4 ± 21.6 M−1) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. Conclusion: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the influence of tartaric acid (TTA) on the bioadhesive, moisture sorption, and mechanical properties of hot–melt-extruded (HME) hydroxypropyl cellulose (HPC) films containing polymer additives. Two Klucel® EF and LF batches (HPC, MW: 80000 and 95000, respectively) containing the model antifungal drug ketoconazole (one batch of each MW with and without TTA 4%) were prepared into films by HME using a Killion extruder (Model KLB-100). The bioadhesive properties of the HPC films, with and without TTA, were investigated ex vivo on the human nails. The parameters measured were work of adhesion and peak adhesion force (PAF). A statistically significant increase in both the area under the curve (AUC) and PAF was seen for the HME films containing TTA than those without TTA. Moisture content of hot-melt extruded HPC films was determined using thermogravimetric analysis (TGA). TGA data collected at the two-week interval (25°C/60% RH), measured higher moisture content for the TTA-containing films than those without TTA. Tensile strength and percent elongation were determined utilizing a TA.XT2i Texture Analyzer® equipped with a 50-kg load cell, TA-96 grips, and Texture Expert™ software. TTA functioned as an effective plasticizer, increasing percent elongation and decreasing tensile strength of the HPC films. TTA could potentially be a candidate for transnail applications in film devices prepared by hot-melt extrusion technology. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine and compare the bioadhesive profiles of hydroxypropylcellulose (HPC) polymer matrices as a function of ? 9 -tetrahydrocannabinol (THC) content. In addition, the effect of processing temperature on the stability of THC and its extent of degradation to cannabinol (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent. Bioadhesive measurements including peak adhesive force, area under the curve, and elongation at adhesive failure were recorded utilizing the TA.XT2 i Texture Analyzer ™ . Data obtained from these tests at various contact time intervals suggested that the incorporation of THC led to an increase in the bioadhesive strength of the HPC polymer matrices. To determine the stability of THC and the resulting CBN content in the matrices, three different processing temperatures were utilized (120, 160, and 200°C). Post-production High Performance Liquid Chromotography (HPLC) analysis revealed that the processed systems contained at least 94% of THC and the relative percent formation of CBN was 0.5% at 120°C and 0.4% at 160°C compared to 1.6% at 200°C. These findings indicate that the cannabinoid may be a plausible candidate for incorporation into systems utilizing hot-melt extrusion techniques for the development of an effective mucoadhesive transmucosal matrix system for delivery of THC. [ABSTRACT FROM AUTHOR]

The oral mucosal cavity is a feasible, safe, and very attractive site for drug delivery with good acceptance by users. The mucosa is relatively permeable and robust, shows short recovery times after stress or damage, is tolerant to potential allergens, and has a rich blood supply. Moreover, oral mucosal drug delivery bypasses the first-pass effect and avoids presystemic elimination in the gastrointestinal tract. Bioadhesive systems provide intimate contact between a dosage form and the absorbing tissue, which may result in high concentration in a local area and hence high drug flux through the absorbing tissue. The efficacy of oral bioadhesive drug delivery systems is affected by the biological environment and the properties of the polymer and the drug. In the present paper, we review systematically some relevant citations regarding the environment, strategies for oral drug delivery and evaluation, and utilization of the main polymers. [ABSTRACT FROM AUTHOR]

Different types of mucoadhesive polymers, intended for buccal tablet formulation, were investigated for their comparative mucoadhesive force, swelling behavior, residence time and surface pH. The selected polymers were carbopols(CP934, and CP940), polycarbophil(PC), sodium carboxymethyl cellulose(SCMC) and pectin representing the anionic type, while chitosan(Ch) as cationic polymer and hydroxypropylmethyl cellulose(HPMC) as a non-ionic polymer. Results revealed that polyacrylic acid derivatives(PAA) showed the highest bioadhesion force, prolonged residence time and high surface acidity. SCMC and chitosan ensured promising bioadhesive characteristics, whilst HPMC and pectin exhibited weaker bioadhesion. Different polymer combinations as well as formulations were evaluated to improve the mucoadhesive performance of the tablets. Bioadhesive tablet formulations containing either 5% CP934, 65% HPMC and 30% spray-dried lactose or 2% PC, 68% HPMC and 30% mannitol showed optimum mucoadhesion and suitable residence time. SCMC, when formulated individually, exhibited promising bioadhesion, acceptable swelling, convenient residence time and surface pH. In-vivo trials of these formulations proved non-irritative and prolonged residence of the mucoadhesive tablets on human buccal mucosa for 8 to 13 h. [ABSTRACT FROM AUTHOR]

The oral cavity is an attractive site for drug delivery due to ease of administration and avoidance of possible drug degradation in gastrointestinal tract and first-pass metabolism. Buccal drug delivery specifically refers to the delivery of drugs within/through buccal mucosa to affect local/systemic pharmacological actions. This review briefly describes advantages and limitations of buccal drug delivery, anatomical structure of oral mucosa, and methodology in evaluating buccal drug delivery system, focusing on physiology, pharmacology, pathology, and formulation design in line with recent developments in buccal delivery systems. [ABSTRACT FROM AUTHOR]

The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Conventional vaginal formulations are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers. In the present study, assemblies for in vitro measurement of bioadhesive strength and retention characteristics of vaginal formulations have been developed. A modified simulated vaginal fluid (SVFM) was used to simulate vaginal conditions for bioadhesion studies. Cellophane hydrated with SVFM and isolated sheep vaginal mucosa were used as model membranes. The bioadhesive potential of various polymers and their combinations was evaluated. Among the polymers evaluated, xanthan gum (XG), sodium alginate (SA), Polycarbophil (PC), and their combinations (XG + SA and XG + PC) were found to possess significant bioadhesive strength. In retention experiments, XG, SA, and combinations (XG + SA and XG + PC) were retained in isolated sheep vaginal tissue, while PC exhibited poor retention under experimental conditions. Based on the results of the study conducted, XG, SA, and combinations (XG + SA and XG + PC) have been proposed as potential candidates for developing bioadhesive vaginal drug delivery systems. [ABSTRACT FROM AUTHOR]

Buccoadhesives have long been employed to improve the bioavailability of drugs undergoing significant hepatic first-pass metabolism. Diltiazem hydrochloride (DLZ) is also reported to have low oral bioavailability due to an extensive hepatic first-pass effect. Controlled-release buccoadhesive hydrophilic matrices containing DLZ were prepared using a 3² factorial design. Amounts of Carbopol® 934P (CP) and Methocel® K100LV (HPMC) were taken as the formulation variables (factors) for optimizing bioadhesion, and kinetics of dissolution and diffusion. A mathematical model was generated for each response parameter. Bioadhesive strength tended to vary quite linearly in increasing order with increasing amount of each polymer. The drug release pattern for all the formulation combinations was found to be non-fickian, approaching zero-order kinetics. The values of permeation coefficient tended to vary non-linearly with polymer amount, depicting the plausibility of interaction between the two polymers. Suitable combinations of the two polymers provided adequate bioadhesive strength and a fairly regulated release profile up to 10 hr. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings. [ABSTRACT FROM AUTHOR]

The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of didanosine (ddI). The aim of this tablet dosage form is to improve the oral absorption of ddI by delivering it in small doses over an extended period and localizing it in the intestine by bioadhesion. Compressed tablets of ddI using Polyox® WSRN-303, Carbopol® 974P-NF, and Methocel® K4M as the bioadhesive release rate-controlling polymers were prepared. The effect of polymer concentration on the release profile and in vitro bioadhesion of the matrix tablets was studied. Tablet formulations with Polyox WSRN-303 (10%) and Methocel K4M (30%) showed 93 and 90% drug release, respectively, after 12 h. The drug release was found to be linear when fitted in the Higuchi equation (square-root time equation), suggesting zero-order release. Carbopo1974-P-NF was found to inhibit the complete release of ddI because of drug-polymer interaction; hence, is not suitable for formulation of ddI. Drug diffusion and swelling of the polymer (anomalous Fickian release) was found dominant in ddI release. In general, in vitro bioadhesion increased with an increase in polymer concentration. Tablets containing a single polymer can be designed to form hydrogels serving the dual purpose of bioadhesion and sustained release. [ABSTRACT FROM AUTHOR]