Development and Evaluation of Ethosomes Loaded with Zingiber zerumbet Linn Rhizome Extract for Antifungal Skin Infection in Deep Layer Skin.

Skin fungal infection is still a serious public health problem due to the high number of cases. Even though medicines are available for this disease, drug resistance among patients has increased. Moreover, access to medicine is restricted in some areas. One of the therapeutic options is herbal medicine. This study aims to develop an ethosome formulation loaded with Zingiber zerumbet (L.) Smith. rhizome extract for enhanced antifungal activity in deep layer skin, which is difficult to cure. Ethosomes were successfully prepared by the cold method, and the optimized formulation was composed of 1% (w/v) phosphatidylcholine and 40% (v/v) ethanol. Transmission electron microscope (TEM) images revealed that the ethosomes had a vesicle shape with a diameter of 205.6-368.5 nm. The entrapment of ethosomes was 31.58% and could inhibit the growth of Candida albicans at a concentration of 312.5 µg/mL. Finally, the ethosome system significantly enhanced the skin penetration and retention of the active compound (zerumbone) compared with the liquid extract. This study showed that Z. zerumbet (L.) rhizome extract could be loaded into ethosomes. The findings could be carried over to the next step for clinical application by conducting further in vivo penetration and permeation tests.

Enhancing oral absorption of poorly water-soluble herb (Kaempferia parviflora) extract using self-nanoemulsifying formulation.

Kaempferia parviflora, a medicinal herb, treats hypertension and promotes longevity with good health and well-being. Its bioactive component is poorly soluble in water, resulting in poor absorption. This study aimed to enhance the bioavailability of K. parviflora dichloromethane (KPD) extract using a self-nanoemulsifying drug delivery system (SNEDDS). KPD was dissolved in diethylene glycol monoethyl, polyoxyl-35 castor oil and caprylic/capric glyceride, and clear yellow SNEDDS solution was obtained. The methoxyflavone markers were used for content and dissolution analysis. Solid SNEDDS was prepared by stepwise mixing of KPD using a mortar and pestle (1:1 ratio) with five solid carriers: Aerosil® 200, Florite® RE, Neusilin® US2 (NEUS), Fujicalin®, and Neusilin® UFL2. The USP apparatus II with simulated gastric fluid USP (SGF without pepsin, pH 1.2) was used in order to perform the in vitro dissolution. The methoxyflavones dissolution at 60 min from KPD, SEDDS, and SNEDDS/NEUS were approximately 16, 92, and 73%, respectively. The pharmacokinetic profiles of methoxyflavones for oral administration were studied using Wistar rats; the areas under the curve of SNEDDS/NEUS (1.77-fold) and SNEDDS (5.38-fold) were significantly higher than that of KPD. The developed formulations showed good stability after storage for 6 months under accelerated and normal conditions.

Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: An in vitro and in vivo study.

The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin-doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox-triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In vivo anticancer efficacy of coated microbeads was examined in BALB/c mice with murine colon carcinoma. These coated microbeads significantly inhibited the growth of all cell lines. The in vivo study confirmed delivery of DOX to the colorectal tumor site, redox-responsiveness, and anticancer efficacy of coated microbeads. Coated microbeads also effectively inhibited primary tumor growth and suppressed tumor metastases without gross toxicity to the non-target tissue. No noticeable damage was found in mouse GI tissues, indicating lack of DOX toxicity. These novel coated microbeads containing thiolated pectin-DOX conjugate may be a promising vehicle for targeted clinical delivery of DOX to the colorectal cancer site by oral administration.

Thiolated pectin-doxorubicin conjugates: Synthesis, characterization and anticancer activity studies.

In this paper, pectin was cross-linked by a coupling reaction with either thioglycolic acid or cystamine dihydrochloride to form thiolated pectins. The thiolated pectins were then coupled with doxorubicin (DOX) derivative to obtain thiolated pectin-DOX conjugates by two different methods, disulfide bond formation and disulfide bond exchange. The disulfide bond exchange method provided a simple, fast, and efficient approach for synthesis of thiolated pectin-DOX conjugates, compared to the disulfide bond formation. Characteristics, physicochemical properties, and morphology of thiolated pectins and thiolated pectin-DOX conjugates were determined. DOX content in thiolated pectin-DOX conjugates using low methoxy pectin was found to be higher than that using high methoxy pectin. The in vitro anticancer activity of thiolated pectin-DOX conjugates was significantly higher than that of free DOX, in mouse colon carcinoma and human bone osteosarcoma cells, but insignificantly different from that of free DOX, in human prostate cancer cells. Due to their promising anticancer activity in mouse colon carcinoma cells, the thiolated pectin-DOX conjugates might be suitable for building drug platform for colorectal cancer-targeted delivery of DOX.

Improved dissolution of Kaempferia parviflora extract for oral administration by preparing solid dispersion via solvent evaporation.

Kaempferia parviflora, a plant in the family Zingiberaceae, has been used in Thai traditional medicines for treating hypertension and promoting longevity with good health and well-being. However, its limited aqueous solubility and low dissolution restrict its bioavailability. The aim of the study was therefore to improve the dissolution rate of K. parviflora extracted with dichloromethane (KPD) by solid dispersions. Different water-soluble polymers were applied to improve dissolution of KPD. The solid dispersions in different ratios were prepared by solvent evaporation method. Only hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol-polyethylene glycol grafted copolymer (PVA-co-PEG) could be used to produce homogeneous, powdered solid dispersions. Physical characterization by scanning electron microscopy, hot stage microscopy, differential scanning calorimetry and powder X-ray diffractometry, in comparison with corresponding physical mixtures, showed the changes in solid state during the formation of solid dispersions. Dissolution of a selected marker, 5,7,4'-trimethoxyflavone (TMF), from KPD/HPMC and KPD/PVA-co-PEG solid dispersions was significantly improved, compared with pure KPD. The dissolution enhancement by solid dispersion was influenced by both type and content of polymers. The stability of KPD/HPMC and KPD/PVA-co-PEG solid dispersions was also good after 6-month storage in both long-term and accelerated conditions. These results identified that the KPD/HPMC and KPD/PVA-co-PEG solid dispersions were an effective new approach for pharmaceutical application of K. parviflora.

Novel pectin-based nanoparticles prepared from nanoemulsion templates for improving in vitro dissolution and in vivo absorption of poorly water-soluble drug.

The purpose of this study was to improve in vitro dissolution and in vivo absorption of itraconazole (ITZ), a poorly water-soluble drug, by means of novel pectin-based nanoparticles prepared from nanoemulsion templates. Nanoemulsion templates were prepared by a high-pressure homogenization using pectin (i.e., 0.5-3.0%w/w low-methoxyl pectin (LMP), amidated low-methoxyl pectin (ALMP), or high-methoxyl pectin (HMP)) as an emulsifier and chloroform as an oil phase. HMP provided good oil-in-water emulsions with ITZ loaded in the oil phase. The chloroform in nanoemulsions was then removed to produce the suspensions of nanoparticles dispersed in water phase. After lyophilization, the dried core-shell nanoparticles with good properties in terms of redispersibility, dissolution, and stability were obtained. The alteration of ITZ crystallinity was clearly observed from powder X-ray diffractogram while no interaction between ITZ and pectin was found in the nanoparticles. The ITZ-loaded nanoparticles showed high percent drug dissolved, especially those prepared from HMP, and could maintain their good dissolution properties even after 6-month storage. The in vivo absorption study in fasted rats demonstrated that pectin-based nanoparticles prepared from nanoemulsion templates could improve absorption of ITZ, that is, 1.3-fold higher than the ITZ commercial product (p<0.05). Pectin type highly influenced the dissolution properties and also in vivo plasma profile. These findings suggested that HMP-based nanoparticles seem to be a promising formulation due to their high AUC(0-24h) and C(max).

Application of pectin in oral drug delivery.

INTRODUCTION: Biopolymers have been used extensively in the pharmaceutical field. Pectin, a biopolymer, has several unique properties that enable it to be used as an excipient or carrier for oral drug delivery systems. Accordingly, several investigators have identified the benefits of pectin-based delivery systems for oral drug administration. AREAS COVERED: This review first describes the chemical structure, source and production, degree of esterification and gel formation properties of pectin. The application of pectin in various oral drug delivery platforms is also discussed, that is, controlled release systems, gastro-retentive systems, colon-specific delivery systems and mucoadhesive delivery systems. EXPERT OPINION: Pectin from different sources provides different gelling abilities, due to variations in molecular size and chemical composition. Like other natural polymers, a major problem with pectin is inconsistency in reproducibility between samples, which may result in poor reproducibility in delivery characteristics. Scintigraphic studies and in vivo studies, in both animals and human volunteers, demonstrate the successful development of a pectin-based colon-specific drug delivery system. Pectin-based controlled release systems, gastro-retentive systems and mucoadhesive systems present promising approaches for increasing the bioavailability of drugs, but are in their infancy. A lack of direct correlation between in vitro release and in vivo absorption studies is a major concern with these systems.

Pectin-based bioadhesive delivery of carbenoxolone sodium for aphthous ulcers in oral cavity.

The objective of this study was to prepare and evaluate the pectin-based dosage form for buccal adhesion. Carbenoxolone sodium, which is used for the treatment of aphthous ulcers in oral cavity, was used as a model drug. The pectin buccal discs were prepared by direct compression. The water uptake and erosion of pectin disc increased progressively with the swelling time. The bioadhesion of dried pectin discs decreased when either the discs were hydrated or the buccal tissue was wet with a small volume of medium. The influencing factors such as pectin type, pectin to lactose ratio, and sweetener type on the formulations were investigated. The results demonstrated that buccal discs prepared from pectin with a high degree of esterification (DE) showed a weaker and more friable characteristic than that with low DE. Decreasing pectin to lactose ratio resulted in the high dissolution rate with low bioadhesive properties. Addition of sweetener in the formulations also affected the hardness, friability, and bioadhesive properties of the discs. The pectin discs containing sweetening agent showed a higher drug release than those without sweetener. The results suggested that pectin-based bioadhesive discs could be used to deliver carbenoxolone sodium in oral cavity.

Wax-incorporated emulsion gel beads of calcium pectinate for intragastric floating drug delivery.

The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

Cryo-scanning electron microscopy (cryo-SEM) as a tool for studying the ultrastructure during bead formation by ionotropic gelation of calcium pectinate.

Understanding the gel ultrastructure is of great importance for process and product development having great effects on the product characteristics. The samples containing high amount of water could not be directly observed using scanning electron microscope (SEM) without removing of water. However, cryo-SEM can be used to study the ultrastructure of hydrated samples. In this study, ultrastructural information of internal structure was obtained by imaging the cryo-fractured beads in a cryo-SEM. This technique was found to be excellent for studying the detailed morphology of structural development and showed better images than normal SEM procedures using freeze-drying for sample preparation. Also, the studies illustrated a morphological change, e.g. from net-like structure to membranous structure caused by syneresis, accompanied by a significant increase in mechanical properties, when the beads are formed by ionotropic gelation. The gelation time of 20 min was found to be the minimum for a complete bead formation, based on the mechanical and SEM data. The results demonstrate the advantageous of cryo-SEM for examining the ultrastructure during bead formation of calcium pectinate.

Improved intestinal absorption of calcitonin by mucoadhesive delivery of novel pectin-liposome nanocomplexes.

Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple mixing of cationic liposomes with pectin solution, in order to improve intestinal absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs were evaluated. The results showed that average particle size of PLNs was significantly larger than that of initial cationic liposomes. The surface charges were shifted from positive to negative after mixing with pectin. The PLNs made of high degree of esterification (DE) pectin showed less negatively charged values than those made of low DE pectin. The entrapment efficiency in cationic liposomes was in the same range even if the drug loading was increased. The in-vivo mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated stronger mucoadhesive properties of PLNs made of low DE pectin, compared to cationic liposomes and PLNs made of other pectins. Moreover, high intensities of a fluorescent marker could be observed throughout the small intestines (i.e. duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after 6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs demonstrated a strong pharmacological action over the eCT solution and eCT-loaded liposomes, in which an enhanced and prolonged reduction in plasma calcium concentration of rats was observed. This was attributed to the ability of pectin to adhere to the mucus layer and prolong retention in the intestinal mucosa.

Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel.

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.

Effect of drug solubility on release behavior of calcium polysaccharide gel-coated pellets.

The aim of this study was to investigate the effect of drug solubility on the release behavior from calcium polysaccharide gel (CaPG)-coated pellets. Three different drugs with similar chemical structure, but different water solubility, namely caffeine (CAF), theophylline (TPL) and theobromine (TBR), were used. Drug-loaded spherical pellets were manufactured by an extrusion-spheronization method. The CaPG was applied on the pellets loaded with different drugs by interfacial complexation coating. The encapsulation efficiency of coated pellets was found to vary from 57.6 to 84.3%, depending on the solubility of the active drug and polysaccharide type. Drug release from different uncoated pellets was relatively unaffected by pH and release media but depended mainly on drug solubility. Release behavior was significantly modified in the pellets coated with CaPG, for all of the drugs tested. Drug release from coated pellets of the different drugs showed different release kinetics. The difference in the drug release is probably due to the difference in the drug dissolution within the core, before its partition and diffusion through the CaPG coat. The CAF dissolved faster and achieved a higher concentration in solution, which drove diffusion. The release of TBR from the coated pellets was much slower than that of the CAF or TPL because of its low solubility. However, the release of all drugs was about four- to sixfold slower for coated than uncoated pellets, suggesting that the coating influenced the retardation of drug release from the coated pellets. Therefore, the CaPG coating may provide a sustained release delivery system for all drugs tested.

Mucoadhesive properties of various pectins on gastrointestinal mucosa: an in vitro evaluation using texture analyzer.

Mucoadhesive performance of various pectins with different degrees of esterification and molecular weights was examined with porcine gastrointestinal (GI) mucosa, i.e. buccal, stomach, small intestine and large intestine, using a texture analyzer equipped with mucoadhesive platform. The instrumental parameters and test conditions such as pre-hydration time of pectin disc, contact time, contact force, test speed of probe withdrawal, GI tissue and test medium were also studied. Two parameters derived from texture analysis, namely maximum detachment force (F(max)) and work of adhesion (W(ad)), were used as parameters for comparison of mucoadhesive performance. The results indicated that degree of hydration of pectin disc affected the mucoadhesive properties. The mucoadhesion of pectin increased with the increased contact time and contact force, but not by the increased probe withdrawal speed. Tissue from different parts of GI tract and test medium also influenced the mucoadhesion. Pectins showed a stronger mucoadhesion on large intestinal mucosa than on small intestinal mucosa. The mucoadhesive properties of pectins on gastric mucosa depended on pH of the medium; a higher F(max) and W(ad) in a pH 4.8 medium than a pH 1.2 medium was revealed. Additionally, pectin showed a significantly higher mucoadhesion than carbomer934P in most of the GI mucosa tested. The results also demonstrated that the mucoadhesive performance of pectins largely depended on their characteristics, i.e. higher degree of esterification and molecular weight gave a stronger mucoadhesion. These findings suggest that pectin can be used as a mucoadhesive carrier for GI-mucoadhesive drug delivery systems.

Swelling and erosion of pectin matrix tablets and their impact on drug release behavior.

The aim of this study was to investigate swelling and erosion behaviors of hydrophilic matrix tablets using pectin and their impact on drug release. The matrix tablets were prepared by direct compression using different types of pectin. Swelling and erosion studies of pectin matrix tablets were carried out in various media. The pectin matrix tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. The swelling action of pectin matrices was controlled by the rate of its hydration in the medium. Release studies showed that the swelling and erosion of matrices influenced the drug release. The extent of matrix swelling, erosion and diffusion of drug determined the kinetics as well as mechanism of drug release from pectin-based matrix tablets. The release data showed a good fit into the power law or the Korsmeyer-Peppas equation indicating the combined effect of diffusion and erosion mechanisms of drug release.

Development of polysaccharide gel coated pellets for oral administration 1. Physico-mechanical properties.

Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

A novel gel formation method, microstructure and mechanical properties of calcium polysaccharide gel films.

Hydrophilic gels, formed by the interaction of calcium ions with either sodium alginate or potassium pectinate, can be deposited as a wet coating on to the surface of drug loaded pellets. If the coated pellets are dried, they could be dispensed to a patient in a capsule for oral delivery of the active drug. In contact with the aqueous fluids of the gastrointestinal tract, the gel coat will rehydrate, swell and will sustain the release of active drug from the core. In order to facilitate the development and refinement of this novel coated system, it is beneficial to have a method that can produce free gel films in a manner that closely mimics the way the gel coat is formed and deposited on the pellet surface. Traditional film producing methods would involve the spraying or depositing (by evaporation) the gel forming polysaccharide on to an inert surface, drying it and then exposing the dry film to a solution containing calcium ions. Because the film is dry before it is gelled, it is fundamentally different to the wet gel coats that are deposited on to the pellets. We have developed a method to produce wet gel films and have evaluated different manufacturing conditions in order to optimize the quality of the completed gel film. Additionally, we have used these films to assess the effect that the type of polysaccharide and the environmental conditions experienced during rehydration (pH and ionic strength) has on the mechanical properties and the microscopic morphology of the gel. Irrespective of the rehydration medium, the calcium pectinate gel films were softer, weaker and more porous, than the calcium alginate films. Although calcium alginate gels that were rehydrated in 0.1M NaCl were porous, the same films rehydrated in either water, simulated gastric fluid USP (without pepsin) or 0.1M HCl were stronger and much more dense microscopically. Furthermore, of the four different alginates that were evaluated, those with a high content of guluronic acid saccharides were the strongest but most brittle when rehydrated in water.

Emulsion gel beads of calcium pectinate capable of floating on the gastric fluid: effect of some additives, hardening agent or coating on release behavior of metronidazole.

Emulsion gel (EMG) beads of calcium pectinate capable of floating in the gastric condition were developed using an emulsion-gelation method and their release properties were investigated. Attempts to modify the drug release were made by applying some additives into the starting solution prior to bead formation, by hardening with glutaraldehyde, and by coating with polymer. The metronidazole-loaded EMG beads were found to float on simulated gastric fluid. Increasing the drug to pectin ratio in the beads slowed the drug release from the conventional and the EMG beads. However, the drug release from these beads was rapid, i.e., about 80% of drug loading released within 20-80 min. The additives (PEG10000, glyceryl monostearate and Eudragit L) had a slight, insignificant, effect on the drug release. Using 2% glutaraldehyde as a hardening agent prolonged the drug release. Coating the beads with Eudragit RL significantly sustained the drug release while the beads remained buoyant. The results suggest that EMG beads are suitable as a carrier for intragastric floating drug delivery and that their release behaviour could be modified by hardening with glutaraldehyde or by coating with Eudragit RL.

Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets.

Morphology and buoyancy of oil-entrapped calcium pectinate gel beads.

A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37 degrees C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 microm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery.