Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Exposure to Ranitidine and Risk of Bladder Cancer: A Nested Case-Control Study.

INTRODUCTION: Ranitidine has been shown to contain the carcinogen N-nitrosodimethylamine and increase urinary N-nitrosodimethylamine in humans. We investigated whether ranitidine use is associated with increased bladder cancer risk. METHODS: A nested case-control study was conducted within the Primary Care Clinical Informatics Unit Research database which contains general practice records from Scotland. Bladder cancer cases, diagnosed between 1999 and 2011, were identified and matched with up to 5 controls (based on age, sex, general practice, and date of registration). Ranitidine, other histamine-2 receptor agonists, and proton pump inhibitors were identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for comorbidities and smoking. RESULTS: There were 3,260 cases and 14,037 controls. There was evidence of an increased risk of bladder cancer in ranitidine users, compared with nonusers (fully adjusted OR = 1.22; 95% CI 1.06-1.40), which was more marked with use for over 3 years of ranitidine (fully adjusted OR = 1.43; 95% CI 1.05-1.94). By contrast, there was little evidence of any association between proton pump inhibitor use and bladder cancer risk based on any use (fully adjusted OR = 0.98; 95% CI 0.88-1.11) or over 3 years of use (fully adjusted OR = 0.98; 95% CI 0.80-1.20). DISCUSSION: In this large population-based study, the use of ranitidine particularly long-term use was associated with an increased risk of bladder cancer. Further studies are necessary to attempt to replicate this finding in other settings.

Design of multicomponent indomethacin-paracetamol and famotidine loaded nanoparticles for sustained and effective anti-inflammatory therapy.

Indomethacin is one of the nonsteroidal anti-inflammatory drugs (NSAIDs) that are widely prescribed drug for pain and inflammation. However, its notoriety of causing gastrointestinal effect, low water solubility, and its short half-life would affect patient compliance and its oral absorption and accordingly justify the need to develop a formula with a controlled and sustained release manner in combination with anti-ulcer drugs. Herein, we synthesized indomethacin-paracetamol co-drug loaded in nanoemulsion and encapsulated in famotiditine loaded polycaprolactone (PCL) nanoparticles. The synthesis of the co-drug was achieved by the formation of a hydrolyzable ester between the indomethacin and paracetamol. The synthesized co-drug was preloading in nanoemulsion (Co-NE), which encapsulated into famotidine PCL nanoparticles utilizing the nanoprecipitation approach. The developed nanosystem showed hydrodynamic size less than 200 nm and the zeta potential value above -30 mV. TEM images confirmed the morphological structure of the formed nanoemulsion and the loaded PCL nanoparticles. Stability studies revealed that the developed nanosystem was stable at different temperatures and pHs over 1 month. Moreover, improvement of the solubilities of these three drugs leading to have a controlled-release multicomponent system of both co-drug and famotidine over 3 days. This multicomponent nanoparticle might be a potential platform to overcome the obstacles of NSAIDs, synergize drugs with different mechanisms of actions by co-encapsulating a small-sized nanoemulsion into PCL nanoparticles for reaching the goal of effective anti-inflammatory therapy.

Effectiveness of Opuntia ficus indica L. inermis Seed Oil in the Protection and the Healing of Experimentally Induced Gastric Mucosa Ulcer.

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from Opuntia ficus indica (OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm2), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H2-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.

Swellable and porous bilayer tablet for gastroretentive drug delivery: Preparation and in vitro-in vivo evaluation.

The purpose of this study was to develop a novel gastroretentive drug delivery system with immediate buoyancy and high wet strength. The proposed bilayer tablet was composed of a drug layer and a highly porous and swellable gastroretentive (GR) layer. The highly porous GR layer was prepared by sublimating the volatile materials after compaction with swellable polymers. This pore-forming process decreased the density of the GR layer and enabled the tablet to float immediately on the dissolution media. The GR layer formulation was optimized by comparing the swelling, erosion, and mechanical properties of candidate swellable polymers. The release rates were conveniently controlled by changing the polymer content in the drug layer, while the swelling and floating properties were provided by the GR layer. The application of percolation theory revealed that the polymer content above the estimated threshold was required for a reliable drug release profile. In vivo study in fed beagle dogs confirmed the enhanced gastric retention time of the tablets compared to that of conventional single layer tablets. Taken together, our data suggest that the proposed system can be a promising platform technology with superior GR properties and a convenient formulation process.

Studies on the influence of ß-cyclodextrin derivatives on the physical stability of famotidine.

The usage of Fourier transform infrared spectroscopy, near infrared spectroscopy, differential scanning calorimetry and microscopy is presented in this work focused on the exploration of the effect of CD on the physical stability of famotidine (FAM). The most significant information was achieved by analysis of the second derivatives of near infrared (NIR) spectra recorded. Changes in the shape of spectra derivatives allow to observe the improvement of physical stability of FAM with the usage of various supramolecular systems based on ß-cyclodextrin (CD) derivatives. The comparison was performed with the usage of maltodextrin in FAM mixtures. We found out that ß-cyclodextrin derivatives in the form of physical mixture and inclusion complexes successfully increased the physical stability of famotidine in solid state while maltodextrin does not show positive effect in imparting physical stability to famotidine.

In vitro Spectroscopic studies on drug interaction of cefpodoxime proxetil and H2 receptor blockers.

One of the relatively advance 3rd generation cephalosporins, cefpodoxime proxetil, is being used all-around. Generally, these are used for the cure of infections allied to urinary and respiratory tract. These cephalosporins have showed a remarkable in vitro activity against many strains of bacteria which are resistant to other orally used active medicinal substances. It is the first oral 3rd generation cephalosporin to be used in the cure of skin infections. The practice of H2 receptor antagonists, concerning lots of treatments recommended in patients with different types of ulcers and allergic urticarial condition, is raising hazards of unwanted secondary outcomes and drug interactions. Learning of in-vitro interaction between cefpodoxime poxetil and H2 blockers (Ranitidine, Famotidine and Cimetidine) were examined applying UV/Visible spectrophotometry and Infrared spectrometry. In the existence of H2 receptor blockers, the cefpodoxime proxetil availability was found to be decreased in vitro only under specific conditions. Furthermore, complexes of Cefpodoxime proxetil-H2 receptor antagonists were manufactured approving the interaction of these drugs. Finally, the above mentioned spectrophotometric techniques were employed to examine the complexes formed (Cefpodoxime proxetil-cimetidine, cefpodoxime proxetil-famotidine and cefpodoxime proxetil-ranitidine).

Fabrication of Hierarchical Polymeric Thin Films by Spin Coating Toward Production of Amorphous Solid Dispersion for Buccal Drug Delivery System: Preparation, Characterization, and In Vitro Release Investigations.

The landscape of thin films is continuously evolving as an attractive self-administration mean to drive patient compliance. This work reports incorporation of drugs into various polymeric compositions using spin coating technology to screen amorphous solid dispersion film formation for buccal applications. Polarized light microscopy and differential scanning calorimetry were used for characterization. Physical stability was assessed after films storage at 0% RH/25°C for 6 months. Chlorpheniramine maleate, theophylline, and famotidine were used as model drugs and mixed with Opadry amb II® or Kollicoat IR®. Acryl-EZE II® or Zein was also used as surface (design I) or surface and base polymers (design II). Of all the drug-Opadry combinations, only chlorpheniramine was amorphously dispersed up to 25% (w/w). In contrast, Kollicoat IR® resulted in amorphous dispersions of all the tested drugs, suggesting that it has a better solubilization capacity. Drugs prepared in design II achieved higher in vitro release compared to respective design I, indicating that lower content of Acryl-EZE II® or Zein can decrease drug release over 3 h. It has been also revealed that Zein could improve physical stability of the aged theophylline solid-dispersed films. Release kinetics of model drugs were satisfactory when described by first-order kinetics, facilitated through anomalous transport of both diffusion and polymer swelling.

Assessment of Substrate-Dependent Ligand Interactions at the Organic Cation Transporter OCT2 Using Six Model Substrates.

Organic cation transporter (OCT) 2 mediates the entry step for organic cation secretion by renal proximal tubule cells and is a site of unwanted drug-drug interactions (DDIs). But reliance on decision tree-based predictions of DDIs at OCT2 that depend on IC50 values can be suspect because they can be influenced by choice of transported substrate; for example, IC50 values for the inhibition of metformin versus MPP transport can vary by 5- to 10-fold. However, it is not clear whether the substrate dependence of a ligand interaction is common among OCT2 substrates. To address this question, we screened the inhibitory effectiveness of 20 µM concentrations of several hundred compounds against OCT2-mediated uptake of six structurally distinct substrates: MPP, metformin, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino]ethanaminium (NBD-MTMA), TEA, cimetidine, and 4-4-dimethylaminostyryl-N-methylpyridinium (ASP). Of these, MPP transport was least sensitive to inhibition. IC50 values for 20 structurally diverse compounds confirmed this profile, with IC50 values for MPP averaging 6-fold larger than those for the other substrates. Bayesian machine-learning models of ligand-induced inhibition displayed generally good statistics after cross-validation and external testing. Applying our ASP model to a previously published large-scale screening study for inhibition of OCT2-mediated ASP transport resulted in comparable statistics, with approximately 75% of "active" inhibitors predicted correctly. The differential sensitivity of MPP transport to inhibition suggests that multiple ligands can interact simultaneously with OCT2 and supports the recommendation that MPP not be used as a test substrate for OCT2 screening. Instead, metformin appears to be a comparatively representative OCT2 substrate for both in vitro and in vivo (clinical) use.

New insight into the control of peptic ulcer by targeting the histamine H2 receptor.

Peptic ulcer disease is one of the major challenges in public health globally and new evidence shows that it can be controlled by targeting the histamine H2 receptor (H2 R). Recently, a number of H2 R antagonists have been synthesized and used to block the action of histamine on the parietal cells in the stomach and decrease the acid production. In this study, we modeled the H2 R by homology modeling using the 3-D crystal structure and this model was validated based on free energy and amino acid residues present in the allowed regions of a Ramachandran plot. We used this 3-D model for screening of highly potent drugs using molecular docking. We found cimetidine, cimetex, and famotidine as the most potent drugs based on the binding affinity of drug-protein interactions. We also generated a cellular network for H2 R that could be useful for better understanding of cellular mechanism and drug targets. These findings provide a new insight into the development of suitable, specific, and effective anti-ulcer drugs for a most effective treatment of ulcerous diseases.

Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

PURPOSE: Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated. METHODS: Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC. RESULTS: Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO. CONCLUSIONS: Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.

The Effect of H2 Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy.

The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H+, K+-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.

Controlled-release nanoencapsulating microcapsules to combat inflammatory diseases.

The World Health Organization (WHO) has reported that globally 235 million people suffer from chronic and other inflammatory diseases. The short half-lives of nonsteroidal anti-inflammatory drugs (NSAIDs) and their notoriety in causing gastrointestinal discomforts, warrants these drugs to be released in a controlled and sustained manner. Although polymeric particles have been widely used for drug delivery, there are few reports that showcase their ability in encapsulating and sustaining the release of NSAIDs. In this paper, polymeric nanoencapsulating microcapsules loaded with NSAIDs were fabricated using solid/water/oil/water emulsion solvent evaporation method. Two NSAIDs, ibuprofen and naproxen, were first pre-loaded into nanoparticles and then encapsulated into a larger hollow microcapsule that contained the third NSAID, celecoxib. A high encapsulation efficiency (%) of these NSAIDs was achieved and a sustained release (up to 30 days) of these drugs in phosphate-buffered saline was observed. Then, a gastrointestinal drug - cimetidine (CIM) - was co-loaded with the NSAIDs. This floating delivery system exhibited excellent buoyancy (~88% up to 24 h) in simulated gastric fluid. It also allowed a sequential release of the drugs, whereby an immediate release of CIM followed by NSAIDs was observed. Drug release of the NSAIDs observed Fickian diffusion mechanism, whereas CIM observed non-Fickian diffusion. Therefore, this delivery system is a promising platform to control the delivery of NSAIDs to combat inflammatory diseases, thereby protecting against possible gastrointestinal side effects that may arise from the overuse of NSAIDs.

Development of a Validated Comparative Stability-Indicating Assay Method for Some H2-Receptor Antagonists.

A comparative force degradation high performance thin layer chromatography (HPTLC) method was developed and validated for some H2-receptor antagonists. The studied H2-receptor antagonists were ranitidine (RAN), nizatidine (NIZ) and famotidine (FAM). The degradation behaviors of the studied H2-receptor antagonists were studied under different stress conditions (hydrolytic, thermal and oxidative) conditions as well as storage conditions according to International Conference on Harmonization (ICH) recommendations. A stability-indicating HPTLC method was optimized in order to separate the analyte from the degradation products formed under various stress conditions. Full separation of the drugs from their degradation products was successfully achieved on an HPTLC precoated silica gel plates. Densitometric measurements were carried out using a Camag TLC Scanner III in the absorbance mode at 320 nm for RAN and NIZ, and 280 nm for FAM. The limits of detection and limits of quantitation range were 5.47-9.37 and 16.30-31.26 ng/band, respectively, for all investigated drugs. The validation studies were performed according to ICH requirements. The developed method was simple, rapid and reliable hence it could be applied for routine quality control analysis of the investigated H2-receptor antagonists in dosage forms. The kinetic behavior, degradation rate constants and half-lives of the degradation of the investigated drugs were studied and compared at different stress conditions. The present study provides, for the first time, a new vision to compare the degradation kinetics of H2-receptor antagonists at the same degradation procedures.

Roxatidine attenuates mast cell-mediated allergic inflammation via inhibition of NF-κB and p38 MAPK activation.

Roxatidine is an active metabolite of roxatidine acetate hydrochloride which is a histamine H2-receptor antagonist that is used to treat gastric and duodenal ulcers. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of roxatidine in phorbol 12-myristate 13-acetate and calcium ionophore (PMACI)-stimulated human mast cells-1 (HMC-1), compound 48/80-induced anaphylactic animal model and chemical allergen-induced contact hypersensitivity (CHS) models. Roxatidine suppressed the mRNA and protein expression of inflammatory cytokines such as TNF-α, IL-6, and IL-1ß in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In addition, roxatidine attenuated PMACI-induced nuclear translocation of NF-κB and the phosphorylation of MKK3/6 and MK2, which are both involved in the p38 MAPK pathway. Furthermore, we observed that roxatidine suppressed the activation of caspase-1, an IL-1ß converting enzyme, in PMACI-stimulated HMC-1 and compound 48/80-induced anaphylactic mice. In CHS model, roxatidine significantly reduced ear swelling, increased number of mast cells, production levels of cytokines and migration of dendritic cells. Our findings provide evidence that the anti-allergic inflammatory properties of roxatidine are mediated by the inhibition of NF-κB and caspase-1 activation, p38 MAPK pathway and mast cell-derived cytokine production. Taken together, the in vitro and in vivo anti-allergic inflammatory effects suggest a possible therapeutic application of roxatidine in allergic inflammatory diseases.

Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study.

The histamine H2-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10³ M(-1), 1.30 (±0.27) × 104 M(-1) and 1.05 (±0.33) × 105 M(-1), respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by ¹H-NMR, UV-visible spectroscopic titrations (including Job plots), electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC), as well as theoretically by molecular dynamics (MD) computation. This study may provide important insights on the supramolecular formulation of H2-receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes.

Molecular modelling studies on 2-substituted octahydropyrazinopyridoindoles for histamine H2 receptor antagonism.

The human histamine H2 receptor (hH2HR) is a G-protein coupled receptor protein with seven transmembrane (TM)-spanning helices primarily involved in regulation of gastric acid secretion. Antagonists targeting hH2HR are useful in the treatment of hyperacidic conditions such as peptic ulcers, gastresophageal reflux disease and gastrointestinal bleeding. We have previously reported the antagonism of 2-substituted pyrazinopyridoindoles at the human histamine H1 receptor and mode of binding of these compounds at the hH1HR using in silico methods. Interestingly, some of the compounds in the series also showed promising activity towards hH2HR that prompted us to investigate the mode of binding of these compounds at hH2HR. In the absence of the crystal structure of hH2HR a homology model has been constructed using multiple sequence alignment, using the X-ray crystal structures of Turkey ß1-adrenergic receptor (tß1AR), Human histamine H1 receptor (hH1HR), Human ß2-adrenergic receptor (hß2AR) and Human D3 dopamine receptor (hD3R). The important residues for binding were depicted in TMIII, TMV, TMVI and TMVII by the homology modelled hH2HR for 2-substituted pyrazinopyridoindoles. A comparative study for deducing the selectivity regarding the binding towards hH1HR and hH2HR has been carried out, which may be useful in designing of selective hH1HR/hH2HR antagonists in these classes of compounds.

Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer.

Exposure of cimetidine (CIM) to dry heat (160-180°C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. One of the products was structurally characterized by mono- and bi-dimensional NMR experiments. It was found to be the N3-enamino tautomer (TAU) of CIM, resulting from the thermal isomerization of the double bond of the cyanoguanidine moiety of the drug, from the imine form to its N3-enamine state. The thus generated tautomer demonstrated to be stable for months in the glassy solid and in methanolic solutions. A theoretical study of CIM and TAU revealed that the latter is less stable; however, the energy barrier for tautomer interconversion is high enough, precluding the process to proceed rapidly at room temperature.

Alginate microspheres obtained by the spray drying technique as mucoadhesive carriers of ranitidine.

The present study is aimed at formulation of alginate (ALG) microspheres with ranitidine (RNT) by the spray drying method. Obtained microspheres were characterized for particle size, surface morphology, entrapment efficiency, drug loading, in vitro drug release and zeta potential. Mucoadhesive properties were examined by a texture analyser and three types of adhesive layers--gelatine discs, mucin gel and porcine stomach mucosa. Microspheres showed a smooth surface with narrow particle size distribution and RNT loading of up to 70.9%. All formulations possessed mucoadhesive properties and exhibited prolonged drug release according to the first-order kinetics. DSC reports showed that there was no interaction between RNT and ALG. Designed microspheres can be considered potential carriers of ranitidine with prolonged residence time in the stomach.