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OBJECTIVES: The aim of the present study was to prepare pectin-hydroxypropyl methylcellulose-coated floating beads for pulsatile release of piroxicam in the treatment of early morning inflammation. MATERIALS AND METHODS: Piroxicam-loaded beads were prepared from sodium alginate and hydroxypropyl methylcellulose (HPMC) in different concentrations of calcium carbonate using the ionotropic gelation method. In order to avoid drug release in the upper part of the gastrointestinal tract, the beads were coated with a pectin-HPMC layer using the dip coating method. Size analysis and encapsulation efficiency, drug loading, in vitro release, swelling behavior, and surface morphology studies of the beads were carried out. RESULTS: The in vitro release study revealed that the pectin-HPMC coating of the beads prevented the release of the drug in an acidic medium and provided pulsed release of the drug after a lag time. Formulation CF4 (containing calcium carbonate in the ratio 3:4 with respect to sodium alginate) exhibited pulsed release of 95.55% at the end of 7 h in phosphate buffer, which was after the desired lag time of 6 h. CONCLUSION: The study revealed that optimized floating pulsatile beads coated with pectin-HPMC can efficiently retain piroxicam in an acidic medium and that there is pulsed release in an alkaline medium after a lag time. It also showed that the beads prepared can potentially be used for chronotherapeutic treatment of the disease associated with early morning inflammation.

Conventional topical delivery in hyperacute bacterial conjunctivitis and endophthalmitis is associated with low drug bioavailability due to rapid precorneal clearance. Hence, in the present investigation, an attempt has been made to enhance ocular bioavailability of tobramycin sulfate by formulating drug-loaded microparticles dispersed in thermosensitive in situ gel.Microparticles prepared by emulsion-ionic gelation technique were characterized for drug loading, entrapment efficiency, particle size, surface morphology, and in vitro drug release. Consequently microparticles (F2 prepared with 1.5%w/v chitosan, 0.2%w/v tripolyphosphate, and drug, 30%w/w of polymer) with high drug loading and encapsulation efficiency were dispersed in thermosensitive in situ gel containing poloxamer 407 and varying percentage of chitosan. In situ gel containing drug-loaded microparticles were evaluated for gelation temperature, rheological behavior, mucoadhesive strength, in vitro drug release, in vitro permeation, ocular irritation, and bioavailability in aqueous humor of rabbits.Formulation containing 17%w/v poloxamer 407 and 0.5%w/v chitosan (P2) gelled at 32°C ± 1.5°C gave pseudoplastic behavior. In vitro permeability of tobramycin from the formulation P2 was found 2-folds greater than eye drops. It also gave significantly higher aqueous humor concentration of tobramycin compared with eye drops with no signs of ocular irritation.Thus, the formulation possesses high potential for treating ocular infections.

Considering the benefits of stomach-specific delivery of H2-antagonists, the objective of the present investigation was to develop and characterize a floating in situ gel containing famotidine–chitosan (FM-CS) microspheres. FM-CS microspheres were prepared using the water-in-oil emulsion technique, with glutaraldehyde as the cross-linking agent. The microspheres were examined for drug loading, entrapment efficiency, particle size, water uptake, in vitro mucoadhesion, in vitro drug release, differential scanning calorimetry and surface morphology. The selected microsphere formulations, F3 (2% w/v CS, DD 81%) and F6 (2% w/v CS, DD 91%), were reconstituted with in situ gel developed using gellan gum. The formulations that were prepared were evaluated for in vitro gelation, in vitro floating behavior, viscosity, and in vitro release characteristics. The in vitro experiments suggested that the formulation G5 (Microsphere formulation F6 reconstituted with in situ gel containing 0.5% w/v gellan gum) remained buoyant and released drug in a sustained manner over 12 h. Thus, formulation G5 can deliver famotidine in a controlled and constant manner over 12 h and can be used for successful stomach-specific delivery of famotidine.

The present investigation was aimed at enhancing the dissolution properties of carvedilol, a poorly water-soluble drug using a combination of solid dispersion and semisolid-filled capsule. The use of lauroyl polyoxyl-6 glycerides as a carrier in a semisolid base to improve the dissolution behaviour of carvedilol was investigated. Solid dispersions containing carvedilol were prepared and percent drug content was assessed. In vitro dissolution studies, Fourier-transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy were used to characterize solid dispersions. Semisolid-filled capsules of carvedilol were prepared using different bases, and their percent drug content and in vitro dissolution behaviour were studied. The optimized solid dispersion containing 3 parts of poloxamer and 0.2 part of Plasdone K90 with respect to 1 part of carvedilol was incorporated into an optimized semisolid base containing 20 parts of lauroyl polyoxyl-6 glycerides with respect to 1 part of carvedilol). The combination of solid dispersions and semisolid-filled capsule produced a significant increase in the rate of release of the drug. The differential scanning calorimetry thermogram of the optimized semisolid formulation did not show carvedilol peak, which suggested that carvedilol had dissolved in the base in the presence of lauroyl polyoxyl-6 glycerides. The dissolution of carvedilol was improved and the lag time of drug release was reduced in the semisolid-filled capsules in which lauroyl polyoxyl-6 glycerides was used as a carrier.

Natural polysaccharides are widely used for development of colon-specific drug delivery systems. The present study was carried out to develop multi-particulate calcium pectinate (Ca-pectinate) formulations for colon-targeted delivery of lornoxicam. The formulations were developed using a combination of polycarbophil and low-methoxy amidated pectin. The beads were prepared using an ionotropic gelation technique. The effects of the polycarbophil and low-methoxy amidated pectin concentrations on the beads characteristics, encapsulation efficiency, swelling study and drug release performance were investigated. The optimized formulation was evaluated for its morphological characteristics. The in vitro drug release of the optimized formulation over a period of 12 h was 96.78 ± 1.35 %. The concentration of the polycarbophil was a decisive factor in sustaining drug release in the colon. The study revealed that optimized Ca-pectinate beads prepared with polycarbophil can efficiently encapsulate lornoxicam. It also showed that these beads can potentially be used for colon-specific delivery of lornoxicam.

The objective of this study was to develop submicron carriers of two drugs that are practically insoluble in water, i.e. meloxicam and aceclofenac, to improve their dissolution behavior. The phase solubility of the drugs was studied using different concentrations of sparingly methylated β-cyclodextrin, Kleptose(®) Crysmeβ (Crysmeb), in the presence and absence of 0.2 % w/v water-soluble chitosan. Drug-loaded submicron particles (SMPs) were prepared using chitosan chlorhydrate and Crysmeb by the ionotropic gelation method. The SMPs were characterized in terms of powder X-ray diffraction, Fourier transforms infrared spectroscopy, size determination, process yield, drug loading, encapsulation efficiency, surface morphology and in vitro release. The drug loading in the SMPs was enhanced in the presence of Crysmeb. The in vitro drug release was found to be enhanced with SMPs prepared using higher concentrations of Crysmeb. These results indicate that SMPs formed from chitosan chlorhydrate and Crysmeb are promising submicron carriers for enhancing the dissolution of meloxicam and aceclofenac.

The physiological constraints imposed by the protective mechanisms of the eye lead to low absorption of drugs and a short duration of the therapeutic effect on ocular drug delivery. Upon instillation of the eye drops only 1–10% of the drug is bioavailable while the rest is drained out of the eye through lacrimal secretions [1]. To overcome this problem various approaches have been reported, such as ointments, inserts and aqueous gels, to increase the ocular residence time of topically applied medication. Controlled drug delivery to the eye offer several advantages over conventional therapies like drug solutions or suspensions as eye drops [2,3]. Ophthalmic inserts offer many advantages over conventional dosage forms, like increased ocular residence, possibility of releasing drugs at a slow and constant rate, accurate dosing, and exclusion of preservatives, increased shelf life and reduced systemic absorption [4–6]. Several reports revealed improved ocular therapy by ophthalmic inserts. Frequency of instillation of gentamycin sulfate was reduced by a long-acting ophthalmic insert [7]. O-butyryl ester prodrug of tilisolol and the O-palmitoyl ester prodrug of tilisolol were incorporated into an ophthalmic insert to control drug release [8]. Di Colo G. and co-researcher [9] observed respective contributions of diffusion and erosion to the release mechanism of drugs, namely prednisolone, oxytetracycline hydrochloride and gentamycin sulphate through erodible ophthalmic inserts based on poly(ethylene oxide). Acyclovir is a polar drug with short plasma half life of 2–3 h [10], therefore 4–5 times application is required when administered as ophthalmic ointment. Also, about 95% of the drug is drained out due to high tear turn-over via nasolacrimal drainage leading to ineffective therapy. Several approaches have been used to improve ocular bioavailabilty of acyclovir. Nanospheres of poly-d,l-lactic acid loaded with acyclovir were prepared and characterized for effect of different formulation parameters. Nanospheres showed a sustained acyclovir release, were highly tolerated by the eye and were able to increase the aqueous humor levels of acyclovir to improve the pharmacokinetic profile [11]. Fresta et al [12] prepared acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres by an emulsion polymerization process in the micellar phase and coated with polyethylene glycol (PEG). Acyclovir-loaded PEG-coated PECA nanospheres were compared with an aqueous solution of the drug for drug levels in aqueous humor. The acyclovir-loaded PEG-coated PECA nanospheres showed 25-fold increase in drug levels in aqueous humor compared with the free drug or the physical mixture. In the present investigation an attempt has been made to prepare ocular inserts of acyclovir capable of releasing drug continuously at controlled rate for 5 days.