Arsenic Trioxide Liposomes: Encapsulation Efficiency and In Vitro Stability

The use of arsenic‐containing compounds in cancer therapy is currently being re‐considered, after the recent approval of arsenic trioxide (Trisenox®) for the treatment of relapsed promyelocytic leukemia (PML). In an attempt to prepare a carrier system to minimize the toxicity of this drug, the aim of this study is to prepare and characterize liposomes encapsulating arsenic trioxide (ATO). For this, we prepared different types of liposomes entrapping ATO: large multilamellar (MLV), sonicated (SUV) and dried reconstituted vesicles (DRV). The techniques used were: thin film hydration, sonication and the DRV method, respectively. Two lipid compositions were studied for each liposome type, EggPC/Chol (1:1) and DSPC/Chol (1:1). After liposome preparation, drug encapsulation was evaluated by measuring arsenic in liposomes. For this, energy‐dispersive X‐ray fluorescence spectroscopy or atomic absorption was used. In addition, the retention of the drug in the liposomes was evaluated after incubating the liposomes in buffer at 37°C. The experimental results reveal that encapsulation of ATO in liposomes ranges between 0.003 and 0.506 mol/ mol of lipid, and is highest in the DRV vesicles and lowest in the small unilamellar vesicles, as anticipated. Considering the in vitro stability of ATO‐encapsulating liposomes: 1) For the PC/Chol liposomes (DRV and MLV), after 24 hours of incubation, more than 70% (or 90% in some cases) of the initially encapsulated amount of ATO was released. 2) The liposomes composed of DSPC/Chol could retain substantially higher amounts of ATO, especially the DRV liposomes (54% retained after 24 h). 3) In the case of PC/Chol, temperature of incubation has no effect on the ATO release after 24 hours, but affects the rate of ATO release in the MLV liposomes, while for the DSPC/Chol liposomes there is a slight increase (statistically insignificant) of ATO release at higher temperature.     

Liposomes of terbutaline sulphate: in vitro and in vivo studies

In vitro studies were conducted to understand the comparative drug diffusion pattern, across artificial membrane, of the drug and of the prepared liposomes of different liposomal membrane composition. In vivo studies were carried out to determine the extent and time-course of pulmonary tissue uptake of administered liposomes containing terbutaline sulphate(TER) on rat lungs. In vitro studies revealed that the drug released from the prepared liposomes obeys Higuchi's diffusion controlled model. Different loading doses and release patterns of drug from the liposomes can be obtained by altering the PC:CHOL ratio and incorporation of cholesterol was found to reduce permeability of the membrane. Similarly drug absorption in vivo in rat's lung following intratracheal instillation, prolonged over 12 hr by liposomal entrapment of TER. The findings of present investigation indicated that liposomally encapsulated TER can be used for pulmonary delivery for maximizing the therapeutic efficacy and reducing undesirable side effects.     

Agglomeration of ibuprofen with talc by novel crystallo-co-agglomeration technique

The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration (CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with talc as an excipient.     

Arsenic trioxide liposomes: encapsulation efficiency and in vitro stability

The use of arsenic-containing compounds in cancer therapy is currently being re-considered, after the recent approval of arsenic trioxide (Trisenox) for the treatment of relapsed promyelocytic leukemia (PML). In an attempt to prepare a carrier system to minimize the toxicity of this drug, the aim of this study is to prepare and characterize liposomes encapsulating arsenic trioxide (ATO). For this, we prepared different types of liposomes entrapping ATO: large multilamellar (MLV), sonicated (SUV) and dried reconstituted vesicles (DRV). The techniques used were: thin film hydration, sonication and the DRV method, respectively. Two lipid compositions were studied for each liposome type, EggPC/Chol (1:1) and DSPC/Chol (1:1). After liposome preparation, drug encapsulation was evaluated by measuring arsenic in liposomes. For this, energy-dispersive X-ray fluorescence spectroscopy or atomic absorption was used. In addition, the retention of the drug in the liposomes was evaluated after incubating the liposomes in buffer at 37 degrees C. The experimental results reveal that encapsulation of ATO in liposomes ranges between 0.003 and 0.506 mol/ mol of lipid, and is highest in the DRV vesicles and lowest in the small unilamellar vesicles, as anticipated. Considering the in vitro stability of ATO-encapsulating liposomes: 1) For the PC/Chol liposomes (DRV and MLV), after 24 hours of incubation, more than 70% (or 90% in some cases) of the initially encapsulated amount of ATO was released. 2) The liposomes composed of DSPC/Chol could retain substantially higher amounts of ATO, especially the DRV liposomes (54% retained after 24 h). 3) In the case of PC/Chol, temperature of incubation has no effect on the ATO release after 24 hours, but affects the rate of ATO release in the MLV liposomes, while for the DSPC/Chol liposomes there is a slight increase (statistically insignificant) of ATO release at higher temperature.     

Energetics of liposomes encapsulating silica nanoparticles

Nanoparticles may be taken up into cells via endocytotic processes whereby the foreign particles are encapsulated in vesicles formed by lipid bilayers. After uptake into these endocytic vesicles, intracellular targeting processes and vesicle fusion might cause transfer of the vesicle cargo into other vesicle types, e.g., early or late endosomes, lysosomes, or others. In addition, nanoparticles might be taken up as single particles or larger agglomerates and the agglomeration state of the particles might change during vesicle processing. In this study, liposomes are regarded as simple models for intracellular vesicles. We compared the energetic balance between two liposomes encapsulating each a single silica nanoparticle and a large liposome containing two silica nanoparticles. Analytical expressions were derived that show how the energy of the system depends on the particle size and the distance between the particles. We found that the electrostatic contributions to the total energy of the system are negligibly small. In contrast, the van der Waals term strongly favors arrangements where the liposome snugly fits around the nanoparticle(s). Thus the two separated small liposomes have a more favorable energy than a larger liposome encapsulating two nanoparticles.     

Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study

The present study was designed to develop and compare acyclovir containing nano-vesicular liposomes and niosomes based on cholesterol, soya L-alpha-lecithin and nonionic surfactant, span 20. The effort was made to study in vitro whether acyclovir-loaded nanovesicles could sustain the release of the drug by increasing residence time and thus, acyclovir could reduce its dose-related systemic toxicity. There were good vesicular distributions in both of the niosomes and the liposomes. The obtained vesicles were within 1 microm and about 35% of them were within a size of 100 nm. The percentage of drug loading varied and the niosomal vesicles contained more drug as compared with the liposomes. When the in vitro drug release was compared, it was found that the liposomes released about 90% drug in 150 min whereas the drug release was just 50% from the niosomal vesicles in 200 min. Again, the niosomes showed better stability compared with the liposomes. Thus, niosome could be a better choice for intravenous delivery of acyclovir.     

A POLAROGRAPHIC METHODOLOGY FOR CONTINUOUS NON-DESTRUCTIVE MONITORING OF DRUG RELEASE FROM LIPOSOMES

A simple methodology based on the differential pulse polarography (DPP) was developed for non-destructive monitoring of drug release from liposomes. The methodology was also capable of determining not only the released material that remained free in the liposomal suspension but also the amount of the drug which was eventually adsorbed on the vesicles surface after its release from the liposomes. Based on this methodology the release kinetics of encapsulated chlorothiazide in 5 mg ml^?1 DRV liposomes was studied at 37°C at pH 7.4. The results were compared to those obtained by centrifuging the DRV sample and measuring the free drug in the supernatant solution with UV-spectroscopy. Approximately 70% of the initially encapsulated drug were released within 24 h of which ca. 46% were subsequently adsorbed on vesicles' surface.     

Ciprofloxacin as Ocular Liposomal Hydrogel

The purpose of this study was to prepare and characterize an ocular effective prolonged-release liposomal hydrogel formulation containing ciprofloxacin. Reverse-phase evaporation was used for preparation of liposomes consisting of soybean phosphatidylcholine (PC) and cholesterol (CH). The effect of PC/CH molar ratio on the percentage drug encapsulation was investigated. The effect of additives such as stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively, were studied. Morphology, mean size, encapsulation efficiency, and in vitro release of ciprofloxacin from liposomes were evaluated. For hydrogel preparation, Carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency of 73.04 ± 3.06% was obtained from liposomes formulated with PC/CH at molar ratio of 5:3 and by increasing CH content above this limit, the encapsulation decreased. Positively charged liposomes showed superior entrapment efficiency (82.01 ± 0.52) over the negatively charged and the neutral liposomes. Hydrogel containing liposomes with lipid content PC, CH, and SA in molar ratio 5:3:1, respectively, showed the best release and transcorneal permeation with the percentage permeation of 30.6%. These results suggest that the degree of encapsulation of ciprofloxacin into liposomes and prolonged in vitro release depend on composition of the vesicles. In addition, the polymer hydrogel used in preparation ensure steady and prolonged transcorneal permeation. In conclusion, ciprofloxacin liposomal hydrogel is a suitable delivery system for improving the ocular bioavailability of ciprofloxacin.     

Double-liposome - based dual-drug delivery system as vectors for effective management of peptic ulcer

The aim of the present investigation was to prepare and evaluate a vesicular dual-drug delivery system for effective management of the mucosal ulcer. Inner encapsulating and double liposomes were prepared by the glass-bead and reverse-phase evaporation methods, respectively. The formulation consisted of inner liposomes bearing ranitidine bismuth citrate (RBC) and outer liposomes encapsulating amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency, and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC of 93.6 ± 1.9 and 84.1 ± 0.9%, respectively, at the end of 144 hours. Ex vivo studies were conducted on Helicobacter pylori (ATCC26695) bacterial cell lines. Double liposomes showed a more enhanced percent H. pylori growth inhibition than the plain drug combination. Further, in vivo studies illustrated enhanced antisecretory and ulcer-protective activity of double liposomes, as compared to the plain drug combination. Microscopic studies also supported the ulcer-protective action of the formulation. Thus, it may be concluded that double liposomes are instrumental in reducing gastric secretions and targeting ulcer sites with the interception of minimal side effects, thus suggesting their potential in ulcer therapy.     

Liposomes for (trans)dermal drug delivery: the skin-PVPA as a novel in vitro stratum corneum model in formulation development

Penetration potential of vesicles destined for trans(dermal) administration remains to be of great interests both in respect to drug therapy and cosmetic treatment. This study investigated the applicability of the phospholipid vesicle-based permeation assay (PVPA) as a novel in vitro skin barrier model for screening purposes in preformulation studies. Various classes of liposomes containing hydrophilic model drug were examined, including conventional liposomes (CLs), deformable liposomes (DLs) and propylene glycol liposomes (PGLs). The size, surface charge, membrane deformability and entrapment efficiency were found to be affected by the vesicle lipid concentration, the presence of the surfactant and propylene glycol. All liposomes exhibited prolonged drug release profiles with an initial burst effect followed by a slower release phase. The permeation of the drug from all of the tested liposomes, as assessed with the mimicked stratum corneum – PVPA model, was significantly enhanced as compared to the permeability of the drug in solution form. Although the DLs and the PGLs exhibited almost the same membrane elasticity, the permeability of the drug delivered by PGLs was higher (6.2?×?10^?6?cm/s) than DLs (5.5?×?10^?6?cm/s). Therefore, this study confirmed both the potential of liposomes as vesicles in trans(dermal) delivery and potential of the newly developed skin-PVPA for the screening and optimization of liposomes at the early preformulation stage.     

Targeting of Antibiotics in Bacterial Infections Using Pegylated Long-Circulating Liposomes

Abstract

PEGylated long-circulating liposomes were used as a delivery system of antibiotics providing enhancements in antibiotic pharmacokinetics and penetration to infected sites. Pharmacokinetic and therapeutic efficacy studies were performed in the model of unilateral pneumonia/septicemia caused by Klebsiella pneumoniae in rats with intact host defense or leukopenic rats. Gentamicin was encapsulated in PEGylated liposomes designed to achieve delivery of antibiotic to the infected left lung tissue. Our data show that the efficacy of liposomal gentamicin was superior to free gentamicin particularly in difficult to treat infection due to impaired host defense (leukopenia) or low antibiotic susceptibility of the infectious organism. In leukopenic rats infected with a high gentamicin-susceptible bacterial strain, free gentamicin must be administered at the maximum tolerated dose to be therapeutically effective. The addition of a single dose of liposome-encapsulated gentamicin on the first day of treatment with free gentamicin leads to full therapeutic efficacy while keeping the antibiotic doses low. In even more difficult to treat infection due to both an impaired host defense (leukopenia) and low gentamicin-susceptibility of the bacterial strain, free gentamicin is not effective, and the addition of the liposome-encapsulated form of gentamicin is needed to achieve full therapeutic efficacy. In this respect, the lipid composition of the liposomes is an important determinant in establishing both sufficient antibiotic levels in blood and sufficient release of antibiotic from the liposomes at the infectious focus.

Ciprofloxacin was encapsulated in PEGylated liposomes designed to serve as a microreservoir of antibiotic during circulation in blood. Our data show that the administration of ciprofloxacin in the liposomal form resulted in slow release of ciprofloxacin from the liposomes over time in blood. Delayed ciprofloxacin clearance, as well as increased and prolonged ciprofloxacin concentrations in blood and tissues was observed. The therapeutic efficacy of liposomal ciprofloxacin was superior to that of free ciprofloxacin. PEGylated liposomal ciprofloxacin was well tolerated in relatively high doses (increasing the maximum tolerated dose for free ciprofloxacin), permitting the administration on a once-a-day schedule without loss in therapeutic efficacy.     

Non inflammatory boronate based glucose-responsive insulin delivery systems

Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L). The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.     

Drug release properties of polyethylene-glycol-treated ciprofloxacin-Indion 234 complexes

The polyethylene glycol (PEG) treatment of ciprofloxacin-Indion 234 complex was aimed to retard rapid ion exchange drug release at gastric pH. Ciprofloxacin loading on Indion 234 was performed in a batch process, and the amount of K⁺ in Indion 234 displaced by drug with time was studied as equilibrium constant K_DM. Drug-resin complex (DRC) was treated with aqueous PEG solution (0.5%–2% wt/vol) of different molecular weights (MWs) for 2 to 30 minutes. The PEG-treated ciprofloxacin-Indion 234 complex was evaluated for particle size, water absorption time, and drug release at gastric pH. During drug loading on Indion 234, the equilibrium constant (K_DM) increased rapidly up to 20 minutes with efficient drug loading. Increased time of immersion of the drug resinate in PEG solutions significantly retained higher size particles upon dehydration. The larger DRC particles showed longer water absorption times owing to compromised hydrating power. The untreated DRC showed insignificant drug release in deionized water; while at gastric pH, ciprofloxacin release was complete in 90 minutes. A trend of increased residual particle size, proportionate increase in water absorption time, and hence the retardation of release with time of immersion was evident in PEG-treated DRC. The time of immersion of DRC in PEG-treated DRC. The time of immersion of DRC in PEG solution had predominant release retardant effect, while the effect of molecular weight of PEG was insignificant. Thus, PEG treatment of DRC successfully retards ciprofloxacin ion exchange release in acidic pH.     

Synthesis and characterization of hydroxyapatite-ciprofloxacin delivery systems by precipitation and spray drying technique

This investigation synthesized and characterized hydroxyapatite (HAP) microspheres, agglomerated microspheres, and implants containing ciprofloxacin. This delivery system is to be used as an implantable drug delivery system for the treatment of bone infections. The HAP microspheres were made by chemical precipitation followed by a spray-drying technique. Agglomerated microspheres were prepared by a wet granulation process using a granulator. Implants were prepared by direct compression of the granules on a Carver press. Ciprofloxacin was analyzed by high-performance liquid chromatography. Characterization of the HAP microspheres include particle size, size distribution, physical state of the drug in the microsphere, and microstructure of the drug delivery system before and after in vitro release. The particle size, porosity, and morphology of the microspheres were dependent on viscosity and concentration of the slurry as well as the atomization pressure used during spray drying. Even at the highest drug load (2% wt/wt), the drug was present in a noncrystalline state. The drug release from the agglomerated microspheres was quick and almost complete within 1 hour. However, compressing the same amount of agglomerated microspheres into an implant greatly reduced the rate of ciprofloxacin release. Only 12% (wt/wt) of the drug was released from the implant within 1 hour. The in vitro release of ciprofloxacin from these implants follows a diffusion-controlled mechanism. This method provides a unique way of producing various shapes and drug loads of HAP microspheres that can be easily manufactured on a commercial scale. Published: January 28, 2002.     

Molecular properties of ciprofloxacin-indion 234 complexes

The purpose of this research was to formulate tasteless complexes of ciprofloxacin with Indion 234 and to evaluate molecular properties of drug complexes. The effect of batch and column process, complexation time, temperature, and pH on ciprofloxacin loading on Indion 234 is reported. Drug resin complexes (DRC) were characterized by infrared spectroscopy, thermal analysis, and x-ray diffraction pattern. Ciprofloxacin release from DRC is obtained at salivary and gastric pH and in the presence of electrolytes. The efficient drug loading was evident in batch process using activated Indion 234 with a drug-resin ratio of 1∶1.3. Drug complexation enhanced with pH from 1.2 to 6, while temperature did not affect the complexation process. Infrared spectroscopy revealed complexation of—NH (drug) with Indion 234. DRC are amorphous in nature. Drug release from DRC in salivary pH was insufficient to impart bitter taste. Volunteers rated the complex as tasteless and agreeable. Complete drug release was observed at gastric pH in 2 hours. The drug release was accelerated in the presence of electrolytes. Indion 234 is inexpensive, and the simple technique is effective for bitterness masking of ciprofloxacin.     

Preparation of Spherical Crystal Agglomerates of Naproxen Containing Disintegrant for Direct Tablet Making by Spherical Crystallization Technique

The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant.     

Agglomerated Oral Dosage Forms of Artemisinin/β-Cyclodextrin Spray-Dried Primary Microparticles Showing Increased Dissolution Rate and Bioavailability

Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/β-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water–methanol solution of artemisinin/β-cyclodextrin. β-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while ¹³C-NMR analysis indicated the partial complexation with β-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/β-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.     

Design and evaluation of deformable talc agglomerates prepared by crystallo-Co-agglomeration technique for generating heterogenous matrix

The crystallo-co-agglomeration technique was used to design directly compressible and deformable agglomerates of talc containing the low-dose drug bromhexine hydrochloride (BXH). The process of agglomeration involved the use of dichloromethane as a good solvent and bridging liquid for BXH, water as a poor solvent, talc as diluent, and Tween 80 to aid dispersion of BXH and diluent into the poor solvent. Hydroxypropyl methylcellulose (50 cps) 4% wt/wt was used to impart the desired mechanical strength and polyethylene glycol 6000 5% wt/wt was used to impart the desired sphericity to the agglomerates. Clarity of the supernatant was considered an endpoint for completion of the agglomeration process. The drug-to-talc ratio in optimized batch 1 (BT1) and batch 2 (BT2) was kept at 1:15.66 and 1:24, respectively. The spherical agglomerates obtained were evaluated for topographic, micromeritic, mechanical, deformation, compressional, and drug release properties. The agglomeration yield and drug entrapment for both batches were above 94% wt/wt. Crushing strength and friability studies showed good handling qualities of agglomerates. Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility of agglomerates. Diametral and axial fracture of compacts showed deformation of agglomerates revealing formation of a heterogeneous compact. Drug release was sustained for 9 hours and 5 hours from BT1 and BT2, respectively, in 0.1N HCl. Hence, the crystallo-co-agglomeration technique can be successfully used for obtaining spherical, deformable, and directly compressible agglomerates, generating a heterogeneous matrix system and providing sustained drug release. Published: July 27, 2007     

Encapsulation of ciprofloxacin within modified xanthan gum- chitosan based hydrogel for drug delivery

The aim of the present work was to investigate the preparation of polyelectrolyte hydrogel as potential drug carrier for antibacterial Ciprofloxacin drug (CFX), intended for controlled release formulation. Hydrogel of N-trimehtyl chitosan (TMC)/sodium carboxymethyl xanthan gum (CMXG) was prepared and ciprofloxacin was employed as a model drug to investigate the loading and release performance of the prepared hydrogel. FTIR, DSC, TGA and SEM analysis were used to characterize the TMC/CMXG hydrogel and its CFX loaded hydrogel. The results showed that the ciprofloxacin was successfully incorporated and released from the prepared hydrogel without the loss of structural integrity or the change in its functionality. The encapsulation efficiency of CFX within the prepared hydrogel was found to be increased with increasing the concentration of drug reaching about 93.8 ± 2.1% with concentration of CFX 250 µg/ml. It was shown also that the drug is entrapped within the gel without significant interaction as confirmed from FTIR spectra and DSC analysis. In vitro release study in phosphate buffer saline (PBS), indicated the steady rise in cumulative drug release with the highest release amount, reaching about 96.1 ± 1.8% up to 150 min, whereby the gel with high drug loading efficiency (3.52 ± 0.07%) displayed faster and higher release rate than that of gel containing a smaller amount of drug (0.44 ± 0.01%). The release kinetics of loaded drug followed zero-order kinetics. CFX drug loaded hydrogel showed high activity against the gram positive and gram negative bacterial strains due to the successful released of CFX from the CFX loaded hydrogel into the tested bacterial strains with the highest diameter of inhibition zone against Escherichia coli (67.0 ± 1.0) as compared to reference antibiotic, Gentamicin (28 ± 0.5). Cytotoxicity of the prepared hydrogel was examined in vitro using lung human normal cell lines and showed the highest cell viability (97 ± 0.5%) at concentration up to 50 µg/ml. Consequently, TMC/CMXG hydrogel can be proposed as new controlled release drug delivery system.     

A Ciprofloxacin Extended Release Tablet Based on Swellable Drug Polyelectrolyte Matrices

The aim of this work was the development of extended release tablets of 500 mg of ciprofloxacin based on swellable drug polyelectrolyte matrices (SDPM). A set of complexes of carbomer, ciprofloxacin and sodium, (CB–Cip)₅₀Na _x , having a molar ratio Cip/CB acid groups of 0.5 and variable proportions of Na⁺ was used to prepare SDPM. Characterization of complexes by FT-IR, powder X-ray diffraction and thermal analysis revealed that Cip, in its protonated form, is ionically bonded to the functional groups of CB. Rates of fluid uptake of (CB–Cip)₅₀Na _x matrices as well as Cip release in simulated gastric fluid were modulated by changes in the proportion of Na⁺ incorporated in the complexes. A direct correlation between fluid uptake and delivery rate was observed along the series of matrices. Release rates were modulated from 1.4 mg/min to 25 mg/min in going from (CB–Cip)₅₀Na₁₀ to (CB–Cip)₅₀Na₁₄. The analysis of kinetic data suggest that rates of swelling, ionic pair dissociation and drug diffusion play a role in the kinetic control of delivery. Complexes were satisfactorily prepared and processed together with small amounts of antiadherent and lubricant excipients to obtain a series of extended release SDPM tablets through the current tableting technology processes. Cip release from matrices was widely modulated by the composition of the complexes yielding a flexible system that allows selecting a composition that releases in 120 min 90% of the dose in simulated gastric fluid.