Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes

Background: The aim of this study was to develop chitosan microspheres for nasal delivery of ondansetron hydrochloride (OND). Method: Microspheres were prepared with spray-drying method using glutaraldehyde as the crosslinking agent. Microspheres were characterized in terms of morphology, particle size, zeta potential, production yield, drug content, encapsulation efficiency, and in vitro drug release. Results: All microspheres were spherical in shape with smooth surface and positively charged. Microspheres had also high encapsulation efficiency and the suitable particle size for nasal administration. In vitro studies indicated that all crosslinked microspheres had a significant burst effect, and sustained drug release pattern was observed until 24 hours following burst drug release. Nasal absorption of OND from crosslinked chitosan microspheres was evaluated in rats, and pharmacokinetic parameters of OND calculated from nasal microsphere administration were compared with those of both nasal and parenteral administration of aqueous solutions of OND. In vivo data also supported that OND-loaded microspheres were also able to attain a sustained plasma profile and significantly larger area under the curve values with respect to nasal aqueous solution of OND. Conclusion: Based on in vitro and in vivo data, it could be concluded that crosslinked chitosan microspheres are considered as a nasal delivery system of OND.     

Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo

The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95?±?18.88?µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (C_max?=_?110.1?±54.2?ng/ml) and subsequent slow drug release (C_s(4–54d)=?2.7?±?0.8?ng/ml) in vivo. Small microspheres (5.91?±?2.24?µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (C_max?=_?40.9?±?13.7?ng/ml), whereas the drug release rate from 4 to 54 d was increased (C_s(4–54d)=4.1?±?1.0?ng/ml). By further decreasing the size of microspheres to 3.38?±?0.70?µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.     

Double-walled microspheres loaded with meglumine antimoniate: preparation,characterization and in vitro release study

Objective: The objective of this study was to fabricate double-walled poly(lactide-co-glycolide) (PLGA) microspheres to increase encapsulation efficiency and avoid rapid release of hydrophilic drugs such as meglumine antimoniate.

Methods: In this study, double-walled and one-layered microspheres of PLGA were prepared using the emulsion solvent evaporation technique to better control the release of a hydrophilic drug, meglumine antimoniate (Glucantime®), which is the first choice treatment of cutaneous leishmaniasis. The effect of hydrophobic coating on microspheres' size, morphology, encapsulation efficiency and drug release characteristics was evaluated. Furthermore, the presence of antimony in meglumine antimoniate made it possible to observe the drug distribution within the microspheres' cross section by means of energy dispersive X-ray spectroscopy.

Results: Drug distribution images confirmed accumulation of the drug within the inner core of double-walled microspheres. In addition, these microspheres encapsulated the drug more efficiently up to 87% and demonstrated reduced initial burst and prolonged release compared to one-layered microspheres. These superiorities make double-walled microspheres an optimum candidate for sustained delivery of hydrophilic drugs.

Conclusion: Double-walled microspheres provide some advantages over traditional microspheres overcoming most of their limitations. Double-walled microspheres were found to be more efficient than their corresponding one-layered microspheres in terms of encapsulation efficiencies and release characteristics.     

5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy

5-Fluorouracil (5FU) was successfully entrapped within poly(lactide-co-glycolide) (PLGA) and hydroyapatite (HA) composite microspheres using the emulsification/solvent extraction technique. The effects of HA to PLGA ratio, solvent ratio as well as polymer inherent viscosity (IV) on encapsulation efficiency were investigated. The degradation and drug release rates of the microspheres were studied for 5?weeks in vitro in phosphate buffered solution of pH 7.4 at 37?°C. The drug release profile followed a biphasic pattern with a small initial burst followed by a zero-order release for up to 35?days. The initial burst release decreased with increasing HA content. The potential of HA in limiting the initial burst release makes the incorporation of HA into PLGA microspheres advantageous since it reduces the risk of drug overdose from high initial bursts. The linear sustained drug release profile over the course of 5?weeks makes these 5-FU-loaded HA/PLGA composite microparticles a promising delivery system for the controlled release of chemotherapy drugs in the treatment of cancer.     

In vitro evaluation of the effects of various additives and polymers on nerve growth factor microspheres

Objective: To evaluate the effects of various additives or polymers on the in vitro characteristics of nerve growth factor (NGF) microspheres.

Materials and methods: NGF microspheres were fabricated using polyethylene glycol (PEG), ovalbumin (OVA), bovine serum albumin (BSA) or glucose as protein protectors, and poly(lactide-co-glycolide) (PLGA) or poly(lactic acid) (PLA)/PLGA blends as encapsulation materials.

Results: Encapsulation efficiencies of the NGF microspheres with various additives or polymers were not more than 30%. A comparative study revealed that OVA was somewhat superior over others, and was thus chosen as the protective additive in subsequent experiments. Polymer analysis showed that NGF release from 1:1 PLA (η?=?0.8):PLGA (75/25, η?=?0.45) microspheres lasted for 90?d with a burst release rate of 12.7%. About 40% of the original bioactivity was retained on the 28th day, while 10% was left on the 90th day.

Discussion and conclusion: The combination of OVA as an additive and the PLA/PLGA blend as the coating matrix is suitable for encapsulation of NGF in microspheres for extended release.     

Dual cross-linked chitosan microspheres formulated with spray-drying technique for the sustained release of levofloxacin

Objective: This study was aimed to develop sustained drug release from levofloxacin (LF)-loaded chitosan (CS) microspheres for treating ophthalmic infections.

Significance: Dual cross-linked CS microspheres developed by the spray-drying technique displays significantly higher level of sustained drug release compared with non-cross-linked CS microspheres.

Methods: LF-loaded CS microspheres were prepared using the spray-drying technique, and then solidified with tripolyphosphate and glutaraldehyde as dual cross-linking agents. The microspheres were characterized by surface morphology, size distribution, zeta potential, encapsulation efficiency, and drug release profiles in vitro. The drug quantification was verified and analyzed by high-performance liquid chromatography (HPLC). The structural interactions of the CS with LF were studied with Fourier transform infrared spectroscopy. The effect of various influencing excipients in the formulation of the dual cross-linked CS microspheres on drug encapsulation efficiency and the drug release profiles were extensively investigated.

Result: The microspheres demonstrated high encapsulation efficiency (72.4?～?98.55%) and were uniformly spherical with wrinkled surface. The mean particle size was between 1020.7?±?101.9 and 2381.2?±?101.6?nm. All microspheres were positively charged (zeta potential ranged from 31.1?±?1.32 to 42.81?±?1.55?mV). The in vitro release profiles showed a sustained release of the drug and it was remarkably influenced by the cross-linking process.

Conclusion: This novel spray-drying technique we have developed is suitable for manufacturing LF-loaded CS microspheres, and thus could serve as a potential platform for sustained drug release for effective therapeutic application in ocular infections.     

Controlled release formulation of ranitidine-containing montmorillonite and Eudragit® E-100

Aim: The objective of this work was to illustrate the suitability of montmorillonite (MMT) as a drug delivery carrier, by developing a new clay–drug composite of ranitidine hydrochloride (RT) intercalated in MMT. Methods: The MMT–RT composite was prepared by ion-exchange process. X-ray diffraction and Fourier transform infrared spectra were employed to confirm the intercalation of RT in the MMT interlayers. The prepared MMT–RT hybrid was coated with cationic polymer Eudragit® E-100 by oil-in-water solvent evaporation method. The release processes of RT from MMT–RT and MMT–RT/Eudragit® E-100 were monitored under in vitro condition in the gastric fluid. Results: X-ray diffraction and Fourier transform infrared spectra analysis indicated the intercalation of RT molecules within the clay lattice. The in vitro release studies showed that MMT–RT released RT in a controlled manner. In the case of MMT–RT/Eudragit® E-100, both the release rate and the release percentages noticeably increased in the presence of Eudragit® E-100, because of its effective exchange with intercalated RT molecules. The release kinetics followed parabolic diffusion mechanism. Conclusion: MMT has great potential as a drug delivery carrier with various scenarios. The dosage of the MMT–RT/Eudragit® E-100 can be in the tablet form. The hybrid material and polymer-coated hybrids are microparticles.     

Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

Development of Novel Interpenetrating Network Gellan Gum-Poly(vinyl alcohol) Hydrogel Microspheres for the Controlled Release of Carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

Screening of ionically crosslinked chitosan-tripolyphosphate microspheres using Plackett–Burman factorial design for the treatment of intrapocket infections

Objective: Application of Plackett–Burman factorial design to investigate the effect of processing factors in the fabrication of ionically crosslinked chitosan-tripolyphosphate (CS-TPP) microspheres.

Significance: Microspheres were screened and optimized to provide maximum process yield (PY), encapsulation efficiency (EE), and time for 80% drug release (T_80%) and minimum burst and particles size (PS), for successful application in periodontitis.

Methods: Processing factors viz. method of preparation (MOP), CS, TPP, crosslinking time (CT), agitation (AS), and drying technique (DT) were selected. Solid state characterization was performed by Fourier-Transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Mucoadhesion, cytocompatibility, and stability of microspheres were also evaluated.

Results: Pareto analysis and analysis of variance, screened most significantly (p?Staphylococcus aureus and Escherichia coli, cytocompatibility for L929 cells, and long-term stability.

Conclusions: Therefore, CS-TPP microspheres were found mucoadhesive, safe, stable and provided controlled and prolonged release of drugs. These properties confirmed its high potential and applicability in chronic periodontitis.     

pH-sensitive sodium alginate/calcined hydrotalcite hybrid beads for controlled release of diclofenac sodium

Objective: The aim of this study was to prepare pH-sensitive sodium alginate/calcined hydrotalcite (SA/CHT) hybrid bead with improved the burst release effect of the drug.

Materials and methods: A series of pH-sensitive SA/CHT hybrid beads were prepared by using Ca²⁺ cross-linking in the presence of diclofenac sodium (DS) and SA. The structure and drug loading of the beads were characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The swelling and the drug release of the fabricated beads were investigated by the pH of test medium and CHT content.

Result: The formed positively charged hydrotalcite layers were adsorbed on the negatively charged SA polymer chains through electrostatic interaction and act as inorganic cross-linkers in the three-dimensional network. Compared to pure SA beads, the incorporation of CHT enhanced the drug encapsulation efficiency, improved the swelling behaviors and slowed the drug release from the hybrid beads.

Discussion and conclusions: The electrostatic interaction between hydrotalcite and SA has restricted the movability of the SA polymer chains, and then slowed down swelling and dissolution rates in aqueous solutions. The results provided a simple method to moderate drug release and matrix degradation of the SA beads.     

Preparation and characteristics of erythromycin microspheres for lung targeting

Background: If erythromycin is micronized into microspheres with suitable particle size, it can improve pulmonary drug concentration to maximize its effectiveness and minimize the adverse side effects. Aim: In this study, erythromycin gelatin microspheres (EM-GMS) were prepared and some characteristics of EM‐GMS were investigated. The drug-targeting index (DTI) of EM-GMS was evaluated to predict their potential as a targeted delivery system. Method: Erythromycin was microencapsulated with gelatin by a double emulsion solvent evaporation method. Some characteristics of EM-GMS, including morphology, particle size, in vitro release, and safety were researched. Results: EM-GMS had a spherical shape and smooth surface morphology. The drug loading and encapsulation efficiency of EM-GMS were 13.56 ± 0.25% and 55.82 ± 2.23%, respectively. The release of erythromycin from EM-GMS showed an initial burst and following a sustained release, with an accumulate release of 80% at 4 hours. The EM-GMS was safe since there was no vein irritation and no hemolysis on the erythrocyte of rabbit at 3.5 mg/mL and a LD50 of 173.07 mg/kg. After administering EM-GMS to rabbits, the concentration of erythromycin in lung was 15.92 times higher than that in plasma and the DTI of EM-GMS in lung was 6.65 as compared with erythromycin lactobionate. Conclusions: The preparation technology of EM-GMS for lung targeting was successful and the quality of microspheres was good.     

Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: in vitro and in vivo evaluation

The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 μm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R ²) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC_0−∞, Kel and t_1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.     

Adsorption characteristics of Congo Red onto the chitosan/montmorillonite nanocomposite

A series of biopolymer chitosan/montmorillonite (CTS/MMT) nanocomposites were prepared by controlling the molar ratio of chitosan (CTS) and montmorillonite (MMT). The nanocomposites were characterized by FTIR and XRD. The effects of different molar ratios of CTS and MMT, initial pH value of the dye solution and temperature on adsorption capacities of samples for Congo Red (CR) dye have been investigated. The adsorption capacities of CTS, MMT and CTS/MMT nanocomposite with CTS to MMT molar ratio of 5:1 for CR were compared. The results indicated that the adsorption capacity of CTS/MMT nanocomposite was higher than the mean values of those of CTS and MMT. The adsorption kinetics and isotherms were also studied. It was shown that all the sorption processes were better fitted by pseudo-second-order equation and the Langmuir equation.     

Development and characterization of wheat gluten microspheres for use in a controlled release system

The purpose of this study was the development and characterization of wheat gluten microspheres for use as controlled release devices, and the evaluation of the effect of the addition of poly (ethylene glycol) (PEG). Diltiazem hydrochloride was used as the model drug in the in vitro release essay. The physical–chemical and morphological properties of the microspheres were evaluated, as well as their encapsulation efficiency. Porosity varied with the presence or absence of PEG. The diltiazem encapsulation efficiency was 72.8% and 96.7% for wheat gluten and gluten/PEG 95/05 microspheres, respectively. The DSC and FTIR results indicated interactions between the microparticles and additives used. In the in vitro release tests it was observed that, for all the studied systems, the burst effect occurred in the first 2 h of release and the microspheres prepared with PEG had a faster release rate. In the attempt to elucidate the release mechanism, the systems were treated based on two well known mathematical models: the Higuchi and the power law. It was found that the microsphere release mechanism is not exclusively diffusion-controlled and, probably, the release occurs through a combination of partial diffusion through the swelling matrix and hydrophilic pores.     

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation,characterization, plasma,and kidney pharmacokinetics

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6?±?5.95?nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71?±?3.02%, and the drug loading was 1.56?±?0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma?=?0.586?±?0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.     

PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

Formulation and characterization of ethylcellulose microparticles containing .l-alanyl- l-glutamine peptide

Context: The l-alanyl-l-glutamine peptide (AGP) has been effective to promote acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and the oral administration of AGP is suggested to prevent prolonged hypoglycemia, such as nocturnal hypoglycemia.

Objective: Considering the ability of AGP on glycemia recovery and AGP’s fast metabolism, the aim of current study was to obtain and characterize ethylcellulose microparticles to deliver the drug for a prolonged time.

Materials and Methods: Microparticles were prepared by simple and double emulsification/hardening method and characterized by scanning electron microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro release.

Results and Discussion: Spherical structures with a mean diameter between 9.30?µm and 13.19?µm were formed. TG analysis showed that the thermal stability of AGP was even more increased by encapsulation with ethylcellulose. In addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in a molecular way. Higher values of encapsulation efficiency were observed for the microparticles prepared by double emulsification (57.83–83.67%) than for those prepared by simple emulsification (18.37%). However, the last ones could release the peptide in a quicker and more extensive manner than those prepared by double emulsification.

Conclusion: For the first time, microparticles containing AGP were developed and exhibited prolonged in vitro release as well as protection to the drug, and it could be considered as a dosage form for patients who suffer from insulin-induced hypoglycemia and/or nocturnal hypoglycemia.     

Preparation of alginate–CaCl2 microspheres as resveratrol carriers

Resveratrol-loaded calcium alginate microspheres for prolonged drug release were prepared by ionic gelation of alginate with calcium chloride (CaCl₂). Further, resveratrol-loaded calcium alginate microspheres were developed using two concentrations of alginate (0.5 and 1 % w/v) and CaCl₂ (0.5 and 1 M) and an encapsulator equipped with a 300-μm nozzle. The mean particle size of the microspheres was between 175.52 and 244.03 μm, and an encapsulation efficiency (EE) of over 95 % was observed. FTIR spectroscopy indicated a polyelectrolyte interaction between alginate and CaCl₂; alginate microsphere thermograms were analyzed by differential scanning calorimetry. X-ray diffraction shows the crystalline change of microspheres by cross linking. The release profiles and EE increased depending on the CaCl₂ concentration, and a slow initial burst release was observed on freeze-dried microspheres. These results indicate that resveratrol-loaded calcium alginate microspheres can be used as a potential resveratrol delivery system in the food industry.     

Preparation and Evaluation of Mucin-Gelatin Mucoadhesive Microspheres for Rectal Delivery of Ceftriaxone Sodium

ABSTRACT

Soluble mucin (S-mucin) processed from the small intestines (ileal region) of freshly slaughtered pigs via homogenization, dialysis, centrifugation and lyophilization and its admixtures with type A gelatin were dispersed in an aqueous medium and used to formulate ceftriaxone sodium-loaded mucoadhesive microspheres by the emulsification cross-linking method using arachis oil as the continuous phase. The release profile of ceftriaxone sodium from the microspheres was evaluated in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). The microspheres were further evaluated as possible novel delivery system for rectal delivery of ceftriaxone sodium in rats. Release of ceftriaxone sodium from the microspheres in both release media was found to occur predominantly by diffusion following non-Fickian transport mechanism and was higher and more rapid in SIF than in SGF. The results obtained from this study may indicate that ceftriaxone sodium could be successfully delivered rectally when embedded in microspheres formulated with either type A gelatin alone or its admixtures with porcine mucin; hence providing a therapeutically viable alternative route for the delivery of this acid-labile third generation cephalosporin.