Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices

The purpose of this research was to investigate the potential use of anionick-carrageenan and nonionic hydroxypropyl-methylcellulose (HPMC, K4) to improve the matrix integrity of directly compressed chitosan tablets containing naproxen sodium, an anionic drug. The influence of buffer pH and drug:polymer ratio on the water uptake, matrix erosion, and drug release were studied. The rapid release of naproxen sodium was seen from matrices containing 100% chitosan due to loss in the matrix cohesiveness; whereas, it was relatively slow for matrices containing optimum concentration ofk-carrageenan. In-situ interaction between oppositely charged moieties resulted in the formation of polyelectrolyte complexes with stoichiometric charge ratios of unity. Fourier transform in frared (FTIR) spectroscopy and powder x-ray diffraction (PXRD) data confirmed the importance of ionic bonds in polyelectrolyte complexation. The ionic interactions between polymers were absent in matrices containing HPMC and the integrity of tablets was improved owing to the presence of viscous gel barrier. The reasons for retarded release of naproxen sodium from the chitosan matrices at different pH include poor aqueous solubility of drug, the formation of a rate-limiting polymer gel barrier along the periphery of matrices, the interaction of naproxen sodium with protonated amino, groups of chitosan, and the interaction of ionized amino groups of chitosan with ionized sulfate groups ofk-carrageenan. Published: June 15, 2007     

Effect of Drying Methods on Swelling,Erosion and Drug Release from Chitosan–Naproxen Sodium Complexes

The purpose of this research was to explore theapplication of ionic interactions between naproxen sodium (NS) and chitosan (CH) in complexes (NSC) prepared by tray drying (TD) and spray drying (SD) methods. Drug–polymer ratio (1:1) in the NSC was optimized on the basis of dialysis studies. The particulate systems of NSC were prepared by tray drying (TD) and spray drying (SD) methods. Release retarding polymers were added to the NSC and to the physical mixtures containing NS–CH and their effects on water uptake, matrix erosion and drug release at different pH were compared. Spray dried complexes (SDC) were spherical, free flowing, light and fine amorphous particles in contrast to the crystalline, hard, tenacious, irregularly shaped, denser tray dried complexes (TDC) with poor flowability. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) patterns confirm the conversion of crystalline to high energy amorphous phase suitable for ionic interactions in NSC. Presence of release retarding polymers, kappa carrageenan and hydroxypropylmethylcellulose (HPMC) in the NSC compacts retarded the drug release and improved the matrix integrity. Carrageenan matrices exhibited more retardation than HPMC tablets. FTIR patterns, erosion, swelling and drug release from matrices support ionic interactions between NS and CH in NSC. The reasons for retarded drug release from the chitosan matrices at acidic pH include poor solubility of drug at acidic pH, formation of a rate limiting polymer gel barrier along the periphery of matrices and the ionic interactions between oppositely charged moieties.     

Investigation of the Effects of Hydroalcoholic Solutions on Textural and Rheological Properties of Various Controlled Release Grades of Hypromellose

Hypromellose (hydroxypropyl methylcellulose, HPMC) matrices are widely used in the formulation of sustained release dosage forms. The integrity and performance of an HPMC matrix formulation depends on rapid hydration and gel formation upon ingestion. Due to the recent alert issued by the Food and Drug Administration regarding the potential negative influence of alcoholic beverages on extended release (ER) formulations, several researchers have evaluated the potential influence of hydroalcoholic media on drug release from ER dosage forms. It has been reported that HPMC matrix formulations do not show “dose dumping” in hydroalcoholic media. The purpose of this study was a fundamental investigation on the effect of hydroalcoholic solutions (0–40% v/v ethanol) on textural and rheological properties of different viscosity grades of neat HPMC, as the functional ingredient within a hydrophilic matrix. In general, hydroalcoholic solutions had little effect on gel formation and mechanical properties of hydrated compacts, while the rheological behavior of HPMC showed dependency on the ethanol content of such solutions.     

Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation

In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.KEY WORDS: chlorpheniramine maleate, diclofenac sodium, extended release, ibuprofen, Prosopis africana     

Chitosan-dextran Sulfate Nanoparticles for Delivery of an Anti-angiogenesis Peptide

Summary A novel nanoparticle delivery system has been developed by employing the oppositely charged polymers chitosan (CS) and dextran sulfate (DS), and a simple coacervation process. Under the conditions investigated, the weight ratio of the two polymers is identified as a determining factor controlling particle size, surface charge, entrapment efficiency and release characteristics of the nanoparticles produced. Particles of 223 nm mean diameter were produced under optimal conditions with a zeta potential of approximately −32.6 mV. A maximum of 75% anti-angiogenesis peptide entrapment efficiency was achieved with a CS:DS weight ratio of 0.59∶1. The same nanoparticle formulation also showed slow and sustained peptide release over a period of 6 days. In contrast, the formulation containing a lower ratio of CS:DS (0.5∶1) was found to have reduced entrapment efficiency and more rapid peptide release characteristics. The results of this study suggest that physicochemical and release characteristics of the CS-DS nanoparticles can be modulated by changing ratios of two ionic polymers. The novel CS-DS nanoparticles prepared by the coacervation process have potential as a carrier for small peptides.     

Use of hydrophilic natural gums in formulation of sustained-release matrix tablets of tramadol hydrochloride

The objective of this work was to develop matrix sustained-release tablets of highly water-soluble tramadol HCl using natural gums (xanthan [X gum] and guar [G gum]) as cost-effective, nontoxic, easily available, and suitable hydrophilic matrix systems compared with the extensively investigated hydrophilic matrices (ie, hydroxypropyl methylcellulose [HPMC]/carboxymethyl cellulose [CMC] with respect to in vitro drug release rate) and hydration rate of the polymers. Matrix tablets of tramadol (dose 100 mg) were produced by direct compression method. Different ratios, of 100∶0, 80∶20, 60∶40, 20∶80, 0∶100 of G gum (or X):HPMC, X gum:G gum, and triple mixture of these polymers (G gum, X gum, HPMC) were applied. After evaluation of physical characteristics of tablets, the dissolution test was, performed in the phosphate buffer media (pH 7.4) up to 8 hours. Tablets with only X had the highest mean dissolution time (MDT), the least dissolution efficiency (DE₈%), and released the drug following a zero-order model via swelling, diffusion, and erosion mechanisms. Guar gum alone could not efficiently control the drug release, while X and all combinations of natural gums with HPMC could retard tramadol HCl release. However, according to the similarity factor (f ₂), pure HPMC and H₈G₂ were the most similar formulations to Topalgic-LP as the reference standard. Published: March 17, 2006     

Formulation and In Vitro Evaluation of Salbutamol Sulphate In Situ Gelling Nasal Inserts

The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16–27 mg, drug content was 3.9–4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5–7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH > AL > CMC Na > HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7–23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation.KEY WORDS: in situ gelling inserts, mucoadhesion, nasal delivery, salbutamol sulfate     

Formulation development and in vitro and in vivo evaluation of membrane-moderated transdermal systems of ampicillin sodium in ethanol: pH 4.7 buffer solvent system

The objective of the present study was to develop membrane-moderated transdermal systems of ampicillin sodium and to evaluate them with respect to various in vitro and in vivo parameters. The membrane-type transdermal systems were prepared using a drug with various antinucleant polymers— hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), cellulose acetate phthalate, chitosan, sodium alginate (SA), and sodium carboxymethylcellulose—in an ethanol: pH 4.7 buffer volatile system by the solvent evaporation technique with HPMC as the rate-controlling membrane for all the systems. The swelling properties of the polymers were studied, and drug-polymer interaction studies were performed. The patches were subjected to various physicochemical studies, in vitro release studies, permeation studies, and skin irritation studies. The best patch among the formulations was selected for further in vivo studies. Compared to the other patches, SA exhibited the highest moisture content at 16%; a 21% moisture uptake was found with MC. The release and permeation of the drug from the SA patch was found to be the maximum. The in vivo study of the SA patch exhibited a peak plasma concentration C_max of 126 μg/mL at T_max 4 hours. Hence, it can be concluded that hydrophilic ampicillin sodium can be developed as a transdermal delivery system with SA that is an alternative to intravenous administration and has minimal adverse effects. Published: January 26, 2007     

Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl β-cyclodextrin

Complexation of celecoxib with hydroxypropyl β-cyclodextrin (HPβCD) in the presence and absence of 3 hydrophilic polymers—polyvinyl pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)—was investigated with an objective of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPβCD and on the dissolution rate of celecoxib from the HPβCD complexes. The phase solubility studies indicated the formation of celecoxib-HPβCD inclusion complexes at a 1∶1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPβCD. Solid inclusion complexes of celecoxib-HPβCD were prepared in 1∶1 and 1∶2 ratios by the kneading method, with and without the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation with HPβCD. The celecoxib-HPβCD (1∶2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib. The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPβCD complexes: a 72.60-, 61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and X-ray diffractometry indicated stronger drug amorphization and entrapment in HPβCD because of the combined action of HPβCD and the hydrophilic polymers. Published: September 29, 2006     

Polyelectrolyte Complexes: Interactions between Lignosulfonate and Chitosan

The interactions between high molecular weight chitosans (fraction of acetylated units (F(A)) = 0.10 or 0.50) and lignosulfonates of varying molecular weights (5000-400000 g/mol) and degrees of sulfonation (0.39-0.64) were studied. Lignosulfonates and chitosans form primarily insoluble polyelectrolyte complexes when mixed at pH 4.5, where the polymers are oppositely charged. In contrast, no complex formation occurred at pH 8, as shown by using a chitosan with F(A) = 0.50, which is soluble at this pH. Thus, a positively charged chitosan is a prerequisite for interactions leading to insoluble complexes with lignosulfonates. It is therefore unlikely that complex formation involves the formation of covalent sulfonylamide linkages as proposed in the literature. The composition of the complexes varied to some degree with the mixing ratio and molecular weight of lignosulfonate, but in most cases compact complexes with a sulfonate/amino ratio close to 1.0 were formed, suggesting that all sulfonate groups are accessible for interactions with chitosan. The influence of the ionic strength and temperature on the complex formation and the behavior of the precipitated complexes were in agreement with that expected for classical polyelectrolyte complexes where the associative phase separation is primarily governed by the increase in entropy due to the release of counterions.     

Release Behaviour of Propranolol HCl from Hydrophilic Matrix Tablets Containing Psyllium Powder in Combination with Hydrophilic Polymers

The objective of this study was to investigate the release behaviour of propranolol hydrochloride from psyllium matrices in the presence hydrophilic polymers. The dissolution test was carried out at pH 1.2 and pH 6.8. Binary mixtures of psyllium and hydroxypropyl methylcellulose (HPMC) used showed that an increase in the percentage of HPMC in the binary mixtures caused a significant decrease in the release rate of propranolol. Psyllium–alginate matrices produced lower drug release as compared to when the alginate was the matrix former alone. When sodium carboxy methyl cellulose (NaCMC) was incorporated into the psyllium, the results showed that matrices containing the ratio of psyllium–NaCMC in the 1:1 ratio are able to slow down the drug release significantly as compared to matrices made from only psyllium or NaCMC as retardant agent suggesting that there could be a synergistic effect between psyllium and NaCMC. The double-layered tablets showed that the psyllium and HPMC in the outer shell of an inner formulation of psyllium alone had the greatest effect of protecting the inner core and thus producing the lowest drug release (DE = 38%, MDT = 93 min). A significant decrease in the value of n in Q = kt ⁿ from 0.70 to 0.51 as the psyllium content was increased from 50 to 150 mg suggests that the presence of psyllium in HPMC matrices affected the release mechanism. Psyllium powder had the ability in the combination with other hydrophilic polymers to produce controlled release profiles. Care and consideration should as such be taken when formulating hydrophilic matrices in different combinations.     

The 3-D model: Does time plasticity represent the influence of tableting speed?

The objective of this study is to test the hypothesis that time plasticity (parameterd from 3-D modeling) is influenced by tableting speed. Tablets were produced at different maximum relative densities (ϱ_rel,max) on an instrumented eccentric tableting machine and on a linear rotary tableting machine replicator. Some 3-D data plots were prepared using pressure, normalized time, and porosity according to Heckel. After fitting of a twisted plane, the resulting parameters were analyzed in a 3-D parameter plot. The materials used were dicalcium phosphate dihydrate (DCPD), spray-dried lactose, microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), κ-carrageenan (CAR), and theophylline monohydrate (TheoM). The results show that tableting speed especially influences the parameterd (time plasticity) of the 3-D model for plastically and viscoelastically deforming materials such as MCC, HPMC, CAR, and TheoM. For more plastically deforming materials such as MCC, HPMC, and TheoM, a subtle influence on ω is also visible. The stages of higher densification are affected more than the stages of lower densification. Brittle materials such as DCPD exhibit no influence of tableting speed. The influence of speed on spray-dried lactose is minor. The results are valid for data obtained from an eccentric tableting machine and also for data from a linear rotary tableting machine replicator. Thus, the empirically derived parameter time plasticityd really represents the influence of time.     

Formulation,Physicochemical Characterization,and In Vitro Study of Chitosan/HPMC Blends-Based Herbal Blended Patches

The current work prepared chitosan/hydroxypropyl methylcellulose (HPMC) blends and studied the possibility of chitosan/HPMC blended patches for Zingiber cassumunar Roxb. The blended patches without/with crude Z. cassumunar oil were prepared by homogeneously mixing the 3.5% w/v of chitosan solution and 20% w/v of HPMC solution, and glycerine was used as plasticizer. Then, they were poured into Petri dish and produced the blended patches in hot air oven at 70 ± 2°C. The blended patches were tested and evaluated by the physicochemical properties: moisture uptake, swelling ratio, erosion, porosity, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, and photographed the surface and cross-section morphology under SEM technique. Herbal blended patches were studied by the in vitro release and skin permeation of active compound D. The blended patches could absorb the moisture and became hydrated patches that occurred during the swelling of blended patches. They were eroded and increased by the number of porous channels to pass through out for active compound D. In addition, the blended patches indicated the compatibility of the blended ingredients and homogeneous smooth and compact. The blended patches made from chitosan/HPMC blends provide a controlled release and skin permeation behavior of compound D. Thus, the blended patches could be suitably used for herbal medicine application.KEY WORDS: chitosan, formulation, herbal blended patches, HPMC, Zingiber cassumunar Roxb     

Evaluation of mucoadhesive hydrogels loaded with diclofenac sodium-chitosan microspheres for rectal administration

Considering the advantageous for the rectal administration of non-steroidal anti-inflammatory drugs, the objective of this study was to formulate and evaluate rectal mucoadhesive hydrogels loaded with diclofenac-sodium chitosan (DFS-CS) microspheres. Hydroxypropyl methylcellulose (HPMC; 5%, 6%, and 7% w/w) and Carbopol 934 (1% w/w) hydrogels containing DFS-CS microspheres equivalent to 1% w/w active drug were prepared. The physicochemical characterization revealed that all hydrogels had a suitable pH for rectal application (6.5–7.4). The consistency of HPMC hydrogels showed direct proportionality to the concentration of the gelling agent, while carbopol 934 gel showed its difficulty for rectal administration. Farrow’s constant for all hydrogels were greater than one indicating pseudoplastic flow. In vitro drug release from the mucoadhesive hydrogel formulations showed a controlled drug release pattern, reaching 34.6–39.7% after 6 h. The kinetic analysis of the release data revealed that zero-order was the prominent release mechanism. The mucoadhesion time of 7% w/w HPMC hydrogel was 330 min, allowing the loaded microspheres to be attached to the surface of rectal mucosa. Histopathological examination demonstrated the lowest irritant response to the hydrogel loaded with DFS-CS microspheres in response to other forms of the drug.     

Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release

Two groups of fluconazole mucoadhesive buccal discs were prepared: (a) Fluconazole buccal discs prepared by direct compression containing bioadhesive polymers, namely, Carbopol 974p (Cp), sodium carboxymethyl cellulose (SCMC), or sodium alginate (SALG) in combination with hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC). (b) Fluconazole buccal discs prepared by freeze drying containing different polymer combinations (SCMC/HPMC, Cp/HPMC, SALG/HPMC, and chitosan/SALG). The prepared discs were evaluated by investigating their release pattern, swelling capacity, mucoadhesion properties, and in vitro adhesion time. In vivo evaluation of the buccal disc and in vivo residence times were also performed. Fluconazole salivary concentration after application of fluconazole buccal systems to four healthy volunteers was determined using microbiological assay and high-performance liquid chromatography. SCMC/HPMC buccal disc prepared by direct compression could be considered comparatively superior mucoadhesive disc regarding its in vitro adhesion time, in vivo residence time, and in vitro/in vivo release rates of the drug. Determination of the amount of drug released in saliva after application of the selected fluconazole disc confirmed the ability of the disc to deliver the drug over a period of approximately 5 h and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.     

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, withr=0.976 andr=0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.     

Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology

The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS), and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 3² full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations, which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced ≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized level; however, furthers increase in its concentration decreased drug dissolution. Published: April 6, 2007     

Reduced Ulcerogenic Potential and Antiarthritic Effect of Chitosan–Naproxen Sodium Complexes

The purpose of this research was to address the utility of naproxen sodium–chitosan spray-dried complexes for antiulcer and antiarthritic activities. The cold stress technique was used to examine the ulcerogenic potential of naproxen sodium (NPX) and spray-dried formulations in the different doses. The ulcerations reduced with the dose of spray-dried complexes of naproxen sodium and chitosan. The conspicuous hemorrhagic lesions were visible in the morphological features of the animal treated with naproxen 50 mg/kg (p.o.). Thus, the results suggest that the spray-dried naproxen sodium–chitosan complex (NPXF) was not corrosive to the gastric mucosa at high doses of 50, 100, and 200 mg/kg (p.o.) under stressful conditions. It is evident from the present investigation that NPXF does not possess any ulcerogenic potential in comparison to naproxen which, under stressful conditions, led to the hypersecretion of HCl, culminating to petichial hemorrhages in the gastric mucosa of the animals. The biphasic pattern was observed in the various arthritic parameters. The rise in paw volume, joint diameter, WBC count, arthritis score, and fall in body weight was significantly ameliorated in the animals treated with NPXF (5, 10, and 20 mg/kg, p.o). At the end of the study, slight erythema was visible in the naproxen-treated animals. However, no erythema, redness, or ulcers were visible in the animals treated with NPXF. Thus, the direct compression properties and reduced ulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability toward the drug, make naproxen sodium–chitosan spray-dried complexes particularly suitable for developing a reduced-dose, fast-release, solid oral dosage form of naproxen.Key words: antiarthritic, chitosan complexes, ulcer     

Modification of theophylline release with alginate gel formed in hard capsules

The aim of this work was to establish whether alginate gel formed spontaneously in hard gelatin capsules which modifies release of a model drug, theophylline. The effects of the alginate composition, the calcium addition, and the dissolution medium on drug release were also investigated. After the capsule shell dissolved in water, at neutral pH the gel layer of sodium alginate was formed immediately as the sodium alginate hydrated and swelled on contact with the aqueous medium. In acidic pH, the contents remained intact and the matrix shape was the same. Theophylline release from capsules containing different grades of alginate demonstrated different release patterns, depending on alginate composition and the pH of the medium. The capsules containing sodium/calcium salts of alginate showed the slowest drug release at neutral pH but the fastest in acidic medium. The presence of calcium acetate in the formulations influenced the drug release kinetics. The drug release in acidic medium showed a non-Fickian diffusion-controlled release, while those in water at neutral pH exhibited a Super Case II transport mechanism. The study also provides evidence that the behavior of alginate in forming the hydrated gel layer may explain the drug release behavior at different pHs. Published: July 6, 2007     

Release Mechanisms Behind Polysaccharides-Based Famotidine Controlled Release Matrix Tablets

Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene foam powder. Polysaccharides (κ-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (κ-carrageenan and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose) were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior, matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from the retardation in drug release and change in its mechanistics.