Development and evaluation of mucoadhesive buccal dosage forms of lidocaine hydrochloride by ex-vivo permeation studies.

Intraoral lidocaine formulations are applied in children and adults for pain relief. The potential risks associated with orally administered lidocaine due to accidental ingestions were highlighted in a warning letter by the US Food and Drug Administration (FDA). This increases the urgency for a need of a child-appropriate dosage forms. For risk minimization, a novel buccal composite dosage form was developed consisting of a lidocaine containing minitablet centered on top of a bilayered mucoadhesive buccal film, so called composite. The preparation included direct tableting of minitablets as well as film-casting technique. Within a comparability study, the permeation of this composite was classified against marketed lidocaine gel, a single-layer film, and a minitablet. These ex-vivo permeation studies under physiologically related conditions in combination with LC-MS/MS quantification enabled the evaluation of permeation in clinically relevant short-term application. The composite showed comparable permeation to marketed gel (104.26 ± 30.15 µg/cm2 vs 128.17 ± 12.49 µg/cm2 cumulative amount of drug) and a higher permeation compared to film (25.84 ± 6.01 µg/cm2). Therefore, a controlled drug application can be assumed by the composite, whereby the risk of inadvertent swallowing as well as uncontrolled absorbed amount of drug substance may be substantially minimized.

Cold Flow Evaluation in Transdermal Drug Delivery Systems by Measuring the Width of the Oozed Adhesive.

The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed adhesive around the original sample was suggested to be an index that properly describes the relationship between the load per unit area and the extent of CF. Further, it was clarified that the average CF width over the entire circumference of the sample was the same whether the samples were round or square as long as the sample area and load were the same. We also observed a linear relationship between the CF width and the aspect ratio of oval and rectangular samples. These results indicated that the CF properties of typical TDDS products lacking CF-proof processing at the edges could be determined by testing samples cut from the product rather than the whole TDDS patch. The proposed width measuring method was simple and useful for optimizing the composition of the adhesive and for testing the quality of the product.

Optimization and Evaluation of the Thermosensitive In Situ and Adhesive Gel for Rectal Delivery of Budesonide.

Budesonide is a glucocorticoid for the treatment of ulcerative colitis (UC). The current study aims to develop a thermosensitive in situ and adhesive gel for rectal delivery of budesonide. HPMC K4M was selected as the adhesive agent based on the adhesive force and the effect on gel performance. The formulation of gel was optimized by using the central composite design-response surface methodology (CCD-RSM); a mathematical model was successfully developed to predict desired formulations as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, and HPMC K4M and the performances of gel. Based on CCD-RSM, a thermosensitive in situ and adhesive gel consisting of 0.002% budesonide, 0.74% HPMC, 4.87% F-68, and 19.0% F-127 was developed. Furthermore, the in vivo behavior of gel was evaluated in Sprague-Dawley rats. In comparison with budesonide solution, rectal administration of budesonide gel at 0.1 mg/kg in rats showed relative bioavailability of 230% with significant increase in rectum uptake.

Mechanical characterization and ex vivo evaluation of anticancer and antiviral drug printed bioadhesive film for the treatment of cervical cancer.

As research progresses on personalized medicines, it is clear that personalized and flexible formulations can provide effective treatment with reduced side effects especially for diseases like cancer, characteristic of high patient variability. 2D and 3D printers are frequently reported in the literature for the preparation of pharmaceutical products with adjusted dose and selected drug combinations. However, in-depth characterization studies of these formulations are rather limited. In this paper, ex vivo and mechanical characterization studies of antiviral and anticancer drug printed film formulations designed for personalized application were performed. Effects of the printing process with pharmaceutical formulations such as paclitaxel (PCX):cyclodextrin (CD) complex or cidofovir (CDV) encapsulated into poly(ethylene glycol)-polycaprolactone (PEG-PCL) nanoparticles on the films were evaluated through a series of mechanical characterization studies. Inkjet printing process was found to cause no significant change in the thicknesses of the film formulations, while mechanical strength and surface free energy increased and nano-sized voids in the film structure decreased. According to the mechanical characterization data, the unprinted film had maximum force (Fmax) value of 15.6 MPa whereas Fmax increased to 43.8 MPa for PCX:CD complex printed film and to 37.7 MPa for the antiviral CDV-PEG-PCL nanoparticle printed film. In the light of ex vivo findings of sheep cervix-uterine tissue, bioadhesive properties of film formulations significantly improved after inkjet printing with different drug formulations. It has also been shown that the anticancer formulation printed on the film was maintained at the cervix tissue surface for >12 h. This study has shown for the first time that inkjet printing process does not adversely affect the mechanical properties of the bioadhesive film formulations. It has also been shown that durable bioadhesive film formulations for personalized dosing can be prepared by combining nanotechnology and inkjet printing.

Propolis-based niosomes as oromuco-adhesive films: A randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers.

Oromuco-adhesive films for buccal delivery of Propolis extract (PPE) entrapped in niosomes, were prepared to treat oral recurrent aphthous ulcer (RAU). PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and in vitro release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7 ± 0.15 µg quercetin equivalents and phenolic content of 180.8 ± 0.11 µg gallic acid equivalents/mg. Multilamellar niosomes of 176-333 nm displayed entrapment efficiency of 91 ± 0.48%, PDI of 0.676 and zeta potential of -4.99. In vitro release after 8 h from niosomal dispersion and films were 64.05% and 29.09 ± 0.13% respectively. Clinical results revealed duration of film adherence from 2-4 h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4-5 h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.

Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films.

PURPOSE: Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS: Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium. RESULTS: SEM revealed lamellar structures within the films, which had a thickness ranging 40-240 µm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60-80% of the total amount of metronidazole was released in 30 min depending on the film formulation. CONCLUSIONS: The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe.

Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida Species Infections.

PURPOSE: Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes. MATERIALS AND METHODS: The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C. albicans ATCC 64124 or HMV4C were assessed in microdilution assays containing water or 1% denture adhesive. The minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) were determined. The cytotoxicities of denture adhesive compounded with these agents were assessed in 1.0 × 105 primary GE keratinocytes in LGM-3 media with resazurin. RESULTS: Lactoferricin B, SMAP28, sphingosine, dihydrosphingosine, and phytosphingosine in 1% denture adhesive lost antimicrobial activity for C. albicans (p < 0.05). Amphotericin B, chlorhexidine dihydrochloride, chlorhexidine gluconate, fluconazole, and nystatin in 1% denture adhesive or compounded directly into denture adhesive and then diluted to 1% adhesive, did not lose antimicrobial activity. Compounded formulations were not cytotoxic (LD50 > 100.0 µg/ml) against primary human GE keratinocytes. CONCLUSIONS: Antimicrobial peptides and antimicrobial lipids had diminished activities in 1% adhesive, suggesting that components in adhesives may inactivate local innate immune factors in the oral cavity, possibly predisposing denture wearers to Candida species infections. More importantly, antifungal agents retained their anti-C. albicans activities in denture adhesive, strongly suggesting that antifungal agents could be candidates for inclusion in adhesive formulations and used as prescribed topical treatments for individuals with denture stomatitis.

A systematic characterization of the factors influencing polymerization and dynamic behavior of n-butyl cyanoacrylate.

INTRODUCTION: Brain arteriovenous malformations are abnormal connections between arteries and veins without an intervening capillary bed. Endovascular glue embolization with N-butyl cyanoacrylate (NBCA) is an accepted form of treatment. The reported complication rates vary widely from 2% to 15%, and timing of polymerization appears to play a major role. Additionally, the interaction between NBCA and vessel surface as well as the presence of biological catalysts are poorly understood. METHODS: Polymerization time was measured for mixtures of Lipiodol/NBCA of 50/50, 70/30, and 60/40. The influence of pH, temperature, and the presence of biological catalysts on polymerization time was investigated. Contact angles were measured on polyvinyl alcohol cryogel (PVA-C), silicone, and endothelial surfaces in a submerged aqueous environment to assess physical surface interactions. High speed video analysis of glue injection through a microcatheter was performed to characterize simulated coaxial flow. RESULTS: NBCA polymerization rate increased with pH and temperature. A hydrophilic surface such as PVA-C was better than silicone at mimicking the physical properties of endothelium. Live endothelium provided a catalytic surface that at least doubled the rate of polymerization. Blood products further increased the polymerization rate in the following order (slowest to fastest): plasma, platelets, red blood cells (RBCs), and lysed RBCs. These factors could explain the discrepancy between in vitro and in vivo results reported in the current literature. High speed video analysis of NBCA injection showed dripping to jetting transition with significant wall effect which deviated from previous ideal assumptions. CONCLUSIONS: The determinants of NBCA polymerization rate are multifactorial and dependent mainly on the presence of biological catalysts coupled with flow related wall interaction.

Melatonin Delivery: Transdermal and Transbuccal Evaluation in Different Vehicles.

PURPOSE: Melatonin (MLT) could be candidate drug for treatment of several diseases because of its high antioxidant and anticarcinogenic activity and its important biological roles. The aim of this study was to assess the influence of different vehicles on the permeation of MLT through buccal and skin tissues. METHODS: Formulations were characterized in terms of rheology, drug release and permeation through human skin as well as porcine buccal mucosa. Irradiation experiments were also performed. RESULTS: The lowest amount of MLT released was from oral adhesive paste Orabase® (OB) and the highest from the emulsion system Montanov® 68 (M68). Skin permeation revealed high pattern for Carbopol® 940 (C940) and M68, and poor for poloxamer 407 (P407) and Pluronic® lecithin organogel (PLO). Statistical differences of MLT remaining in skin between M68 vs C940 (p < 0.05) and M68 vs PLO (p < 0.05) were observed. Transmucosal results showed that sodium carboxymethylcellulose (NaCMC) was the best and OB the worst vehicle. P407 and PLO followed similar behaviour. Photostability studies revealed high percentage of degradation of MLT in solution which was also similar when was loaded in OB. The rest of formulations showed low rates of degradation. CONCLUSIONS: C940 or M68 and NaCMC can be proposed as formulations for a potential systemic effect of MLT by skin and buccal mucosa routes, respectively. However, if the intended objective is to obtain local action in the skin and buccal mucosa, the proposed formulations are M68 or P407 and PLO.

Ex-vivoand in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base.

The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichia coli and Staphylococcus aureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system.

An evaluation of the adhesion of solid oral dosage form coatings to the oesophagus.

There is a requirement for the development of oral dosage forms that are adhesive and allow extended oesophageal residence time for localised therapies, or are non-adhesive for ease of swallowing. This study provides an initial assessment of the in vitro oesophageal retention characteristics of several widely utilised pharmaceutical coating materials. To this end, a previously described apparatus has been used to measure the force required to pull a coated disc-shaped model tablet across a section of excised oesophageal tissue. Of the materials tested, the well-studied mucoadhesive polymer sodium alginate was found to be associated with significant oesophageal adhesion properties that was capable of 'self-repairing'. Hydroxypropylmethylcellulose exhibited less pronounced bioadhesive behaviour and blending this with plasticiser or with low molecular weight polymers and surfactants did not significantly affect this. Low molecular weight water soluble polymers, were found to behave similarly to the uncoated glass control disc. Polysorbates exhibited bioadhesion behaviour that was majorly influenced by the nature of the surfactant. The insoluble polymer ethylcellulose, and the relatively lipophilic surfactant sorbitan monooleate were seen to move more readily than the uncoated disc, suggesting that these may have a role as 'easy-to-swallow' coatings.

Preliminary findings of arterial embolization with balloon-occluded and flow-dependent histoacryl glue embolization in a swine model.

PURPOSE: To evaluate the potential usefulness of the balloon-occluded histoacryl glue embolization (B-glue) technique. MATERIALS AND METHODS: Both flow-dependent (no balloon occlusion) and B-glue techniques were used for 24 intercostal arteries of two female swine. N-butyl 2-cyanoacrylate (NBCA) was diluted with lipiodol to a 50 % solution, which was infused after occluding the arteries with microballoon catheters. The embolization range, fragmentation, reflux, adhesion, and glue particle attachment were compared between flow-dependent and B-glue techniques. RESULTS: The B-glue technique was performed in a controlled fashion resulting in successful arterial occlusion without fragmented migration of the injected glue cast. Reflux occurred less frequently with the B-glue technique and was significantly different (p = 0.039) [Corrected] from that for the flow-dependent technique. Catheters were safely removed from the arterial walls, although in one instance (8.3 %), large glue particles were found to be attached to the catheter tip on removal. Conversely, the flow-dependent technique was more difficult to control and resulted in several instances of higher rates of fragmentation. CONCLUSION: The B-glue technique can efficiently control NBCA delivery with lower rates of reflux.

Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs.

Gellan gum/pectin beads were prepared by ionotropic gelation, using Al(3+) as crosslinker. High yield (92.76%) and entrapment efficiency (52.22-88.78%) were reached. Beads exhibited high circularity (0.730-0.849) and size between 728.95 and 924.56 µm. Particle size and circularity was increased by raising polymer and crosslinker concentrations. Polymers ratio did not influence beads properties. The materials stability and the absence of drug-polymers interactions were evidenced by thermal analysis and FTIR. The high beads mucoadhesiveness was evidenced by in vitro and ex vivo tests. The erosion of beads was greater in acid media while swelling was more pronounced in pH 7.4. Drug release was dependent on pH in which samples 11H1-3, 11H1-5 and 41H1-3 released only 34%, 20% and 22% of ketoprofen in pH 1.2, while in pH 7.4 the drug release was sustained up to 360 min. Korsmeyer-Peppas model demonstrated that drug release occurred according to super case-II transport.

Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.

Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety.

The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161.

Oromucosal delivery of venlafaxine by linseed mucilage based gel: in vitro and in vivo evaluation in rabbits.

Linseed is the crop that is used as a foodstuff in European and Asian countries. The objective of the present work was to extract mucilage from linseed, utilize it as mucoadhesive gelling agent along with synthetic polymers and administration of venlafaxine by buccal route in the gel form. Buccal administration of venlafaxine will avoid first pass metabolism, which will increase the bioavailability of the drug. Linseed mucilage based buccal mucoadhesive gel preparations in combination with chitosan, carbopol 934P, carboxy methylcellulose and polyvinyl pyrrolidone were formulated and the viscosity, gel strength, percentage mucoadhesion and in vitro diffusion of the formulation was evaluated. Formulation (F2) was subjected to in vivo analysis in rabbits. Formulation F2, which contained linseed mucilage (2 %) and chitosan (0.5 %), showed the highest percentage of mucoadhesion, gel strength and sustained drug diffusion. The bioavailability by the oral route and buccal route were compared with that of the intravenous route. The bioavailability of venlafaxine in the formulation F2 was 63.08 ± 1.28 % by buccal route, which was higher than by the oral route (39.21 ± 6.18 %). Based on these results, the combination of linseed mucilage and chitosan can be used to form a buccal mucoadhesive gel and increase the bioavailability of venlafaxine.

Preclinical evaluation of drug in adhesive type ondansetron loaded transdermal therapeutic systems.

The in vivo assessment of percutaneous absorption of molecules is a very important step in the evaluation of any transdermal drug delivery system and a key goal in the design and optimization of transdermal dosage forms lies in understanding the factors that determine a good in vivo performance. The objective of the present investigation is to assess the in vivo performance of an optimized transdermal system of ondansetron hydrochloride in rabbits and to generate preclinical pharmacokinetic data. The pharmacokinetic performance of ondansetron hydrochloride following intravenous and transdermal administration was studied in rabbits following non compartmental pharmacokinetic analysis. The pharmacokinetic parameters such as area under the curve, elimination rate constant, elimination half life and mean residence time, were significantly (P < 0.01) different following transdermal administration compared to intravenous administration. Absolute bioavailability of the transdermal film studied was estimated to be 0.37 ± 0.06 which is quite low because a very high drug loading in the transdermal system was essential to achieve sufficient thermodynamic activity for transdermal permeation. Though in vivo studies in rabbits are found promising, investigations in healthy human subjects are essential to confirm the performance of the developed transdermal films.

In vivo, in vitro evaluation of linseed mucilage based buccal mucoadhesive microspheres of venlafaxine.

The purpose of the present research work was to extract linseed mucilage, use it as a mucoadhesive agent and to develop mucoadhesive microspheres for buccal delivery with an intention to avoid hepatic first-pass metabolism, by enhancing residence time in the buccal cavity. Linseed mucilage was extracted and used to prepare microspheres with varying concentrations of mucilage from formulation F1-F4 (1-2.5%) by spray-drying technique. The microspheres were evaluated for the yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, in vitro drug release, histological study, and stability. Microspheres were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction study. Further, the bioavailability study using the New Zealand rabbits was carried out. Formulation F4 showed the maximum mucoadhesion 89.37 ± 1.35%, 92.10 ± 1.37% incorporation efficiency, highest swelling index 0.770 ± 1.23. F4 showed a marked increase in the bioavailability after buccal administration (51.86 ± 3.95) as compared to oral route (39.60 ± 6.16). Also it took less time to reach maximum plasma concentration of 21.38 ± 1.05 ng/ml as compared to oral solution where it required 180 min to reach maximum plasma concentration of 17.98 ± 1.14. It is concluded from the results that linseed mucilage can be used in the production of the mucoadhesive microspheres.

Bioadhesive sulfacetamide sodium microspheres: evaluation of their effectiveness in the treatment of bacterial keratitis caused by Staphylococcus aureus and Pseudomonas aeruginosa in a rabbit model.

The aim of this study was to prepare bioadhesive sulfacetamide sodium (SA) microspheres to increase their residence time on the ocular surface and to enhance their treatment efficacy on ocular keratitis. Microspheres were fabricated by spray drying method using mixture of polymers such as pectin, polycarbophil and hydroxypropylmethyl cellulose (HPMC) at different ratios. The particle size and distribution, morphological characteristics, thermal behavior, encapsulation efficiency, mucoadhesion and in vitro drug release studies on formulations have been investigated. After optimisation studies, SA-loaded polycarbophil microsphere formulation with polymer:drug ratio of 2:1 was found to be the most suitable for ocular application and used in in vivo studies. In vivo studies were carried out on New Zealand male rabbit eyes with keratitis caused by Pseudomonas aeruginosa and Staphylococcus aureus. Sterile microsphere suspension in light mineral oil was applied to infected eyes twice a day. Plain SA suspension was used as a positive control. On 3rd and 6th days of the antimicrobial therapy, the eyes were examined in respect to clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal oedema and corneal infiltrates) which are the main symptoms of bacterial keratitis and then cornea samples were counted microbiologically. The rabbit eyes treated with microspheres demonstrated significantly lower clinical scores than those treated with SA alone. A significant decrease in the number of viable bacteria in eyes treated with microspheres was observed in both infection models when compared to those treated with SA alone. In conclusion, in vitro and in vivo studies showed that SA-loaded microspheres were proven to be highly effective in the treatment of ocular keratitis.