Effect of high-pressure homogenization on stability of emulsions containing zein and pectin

The aim of this study was to investigate the effect of high-pressure homogenization on the droplet size and physical stability of different formulations of pectin–zein stabilized rice bran oil emulsions. The obtained emulsions, both before and after passing through highpressure homogenizer, were subjected to stability test under environmental stress conditions,that is, temperature cycling at 4 °C/40 °C for 6 cycles and centrifugal test at 3000 rpm for 10 min. Applying high-pressure homogenization after mechanical homogenization caused only a small additional decrease in emulsion droplet size. The droplet size of emulsions was influenced by the type of pectin used;emulsions using high methoxy pectin(HMP) were smaller than that using low methoxy pectin(LMP). This is due to a greater emulsifying property of HMP than LMP. The emulsions stabilized by HMP–zein showed good physical stability with lower percent creaming index than those using LMP, both before and after passing through high-pressure homogenizer. The stability of emulsions after passing through high-pressure homogenizer was slightly higher when using higher zein concentration, resulting from stronger pectin–zein complexes that could rearrange and adsorb onto the emulsion droplets.

Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment

Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin(DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape.However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character;in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors.

Design and characterization of clindamycin-loaded nanofiber patches composed of polyvinyl alcohol and tamarind seed gum and fabricated by electrohydrodynamic atomization

In this study, we developed a polymeric nanofiber patch(PNP) for topical disease treatment using electrohydrodynamic atomization(EHDA). The nanofibers were prepared using various concentrations of polyvinyl alcohol(PVA) and tamarind seed gum and loaded with clindamycin HCl as a model drug. The precursor polymer solutions were sprayed using the EHDA technique; the EHDA processing parameters were optimized to obtain blank and drug-loaded PNPs. The skin adherence, translucence, and ventilation properties of the prepared PNPs indicated that they are appropriate for topical application. The conductivity of the polymer solution increased with increasing PVA and clindamycin concentrations, and increasing the PVA concentration enhanced the solution viscosity. Based on scanning electron microscopy analysis, the PVA concentration had a pronounced effect on the morphology of the sprayed product. Nanofibers were fabricated successfully when the solution PVA concentration was 10%, 13%, or 15%(w/v). The applied voltage significantly affected the diameters of the prepared nanofibers, and the minimum nanofiber diameter was 163.86 nm. Differential scanning calorimetry and X-ray diffraction analyses indicated that the modeldrug was dispersed in PVA in an amorphous form. The PNP prepared with a PVA:gum ratio of 9:1 absorbed water better than the PVA-only PNP and the PNP with a PVA:gum ratio of 9.5:0.5. Moreover, the PNPs loaded with clindamycin at concentrations of 1%–3% prohibited the growth of Staphylococcus aureus more effectively than clindamycin gel, a commercially available product.

A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

To enhance the dissolution of poorly soluble mefenamic acid,self-emulsifying formulation(SEF),composing of oil,surfactant and co-surfactant,was formulated.Among the oils and surfactants studied,Imwitor■ 742,Tween■ 60,Cremophore■ EL and Transcutol■ HP were selected as they showed maximal solubility to mefenamic acid.The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading.The droplet size after dispersion and drug dissolution of selected formulations were investigated.The results showed that the formulation containing Imwitor■ 742,Tween■ 60 and Transcutol■ HP(10:30:60)can encapsulate high amount of mefenamic acid.The dissolution study demonstrated that,in the medium containing surfactant,nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min.In phosphate buffer(without surfactant),80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min,from the commercial product.The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.

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 wellbeing. 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 longterm and accelerated conditions. These results identified that the KPD/HPMC and KPD/PVAco-PEG solid dispersions were an effective new approach for pharmaceutical application of K. parviflora.

Design and characterization of monolaurin loaded electrospun shellac nanofibers with antimicrobial activity

The aim of this study was to elucidate the optimized fabrication factors influencing the formation and properties of shellac(SHL) nanofibers loaded with an antimicrobial monolaurin(ML). The main and interaction effects of formulation and process parameters including SHL content(35%–40% w/w), ML content(1%–3% w/w), applied voltage(9–27 kV) and flow rate(0.4–1.2 ml/h) on the characteristic of nanofibers were investigated through a total of 19 experiments based on a full factorial design with three replicated center points. As a result, the SHL content was the major parameter affecting fiber diameter. Another response result revealed that the SHL content would be also the most significant negative impact on amount of beads. An increase in the concentration of SHL leaded to a reduction in the amount of beads. From the results of characterization study, it was proved that ML might be entrapped between the chains of SHL during the electrospinning process exhibiting an excellent encapsulation. According to the response surface area, small(?488 nm) and beadless(?0.48) fibers were obtained with the SHL and ML contents of 37.5% and 1.1% w/w respectively, at the applied voltage of 18 k V and the flow rate of 0.8 ml/h. In addition, the results of the kill-kinetic studies showed that SHL nanofibers loaded with ML exhibited an excellent antibacterial activity against Staphylococcus aureus, while Escherichia coli was less affected due to the hydrophilic structure of the its outer membrane. ML also exerted an antifun-gal activity by reducing the number of Candida albicans colonies. Based on their structural and antimicrobial properties, SHL nanofibers containing ML could be potentially used as a medicated dressing for wound treatment.

Characterization of recrystallized itraconazole prepared by cooling and anti-solvent crystallization

The objective of the present study was to alter the crystal habit of itraconazole(ITZ)by cooling and anti-solvent crystallization and characterize its properties.ITZ was recrystallized in different solvents and the effects of each solvent on morphology of crystals,dissolution behavior and solid state of recrystallized drug particles were investigated.The results revealed that ITZ crystals recrystallized by cooling and anti-solvent crystallization showed the different crystal habits from the untreated ITZ.Using cooling crystallization tended to provide needle-shaped crystals while the crystals obtained from anti-solvent crystallization showed more flaky,plate shape.This indicated the importance of preparation method on nucleation and crystal growth.No change in drug polymorphism was observed,according to determination of thermal property and crystalline state by differential scanning calorimetry and powder X-ray diffractometry,respectively.The recrystallized ITZ showed higher drug dissolution than untreated ITZ and the highest drug dissolution was observed from the samples recrystallized in the presence of PEG 200,which provided the small plate-shaped crystals with tremendously increased in surface area.However,the increasing of drug dissolution is relatively small,therefore,further development may be required.

Design of porous Eudragit^(■)L beads for floating drug delivery by wax removal technique

The aim of this study was to design porous matrix beads for floating drug delivery using enteric polymer, Eudragit~? L and various amounts of waxes(0, 0.1, 0.5, 1, 2 and 3% w/w). In this study, wax containing cetyl alcohol and white petrolatum was utilized to produce pores using a wax removal technique. To prepare the beads, Eudragit~? L, metronidazole and wax were dissolved in acetone and then extruded into dichloromethane. The effect of the amount of wax on the floating and drug release behavior of the Eudragit~? L beads was determined.After the extruded product was immersed in dichloromethane, wax dissolved out from the formed beads, resulting in a porous structure. The prepared beads could float in simulated gastric fluid for more than 10 hours. Different amounts of wax had an effect on the drug release. We found that when the percentage of wax increased, the drug release was higher while the beads remained floating. The results suggest that Eudragit~? L beads could be used as a carrier for an intragastric floating drug delivery system.

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

Dissolution improvement by solid dispersions composed of nifedipine, Eudragit?E and silica from rice husk

Nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].

Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin

Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specific(targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated(25 °C/60% RH) and long-term(5 °C) stability of DNGs prepared with formaldehyde(FDNGs) and glyoxal(GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared(initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different(p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.

Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents

Solid dispersions of nifedipine(NDP), a poorly water-soluble drug, and amino methacrylate copolymer(AMCP) with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate,titanium dioxide, and mesoporous silica from rice husks(SRH), were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry(PXRD) and differential scanning calorimetry(DSC). The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy(SEM). The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium.The results suggested that solid dispersions containing adsorbents(SRH in particular) demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

Effect of cooling technique on physicochemical properties of ternary solid dispersion of manidipine hydrochloride prepared by melting method

Solid dispersion is an established concept for drug solubility and bioavailability enhancement but strongly dependent on the choice of an appropriate carrier and preparation technique[1,2].Ternary solid dispersion is one of the promising methods to increase the solubility of poorly-water soluble drug.The present work was conducted to increase the solubility of manidipine hydrochloride(MDP)using ternary solid dispersion prepared by melting and then solidifying at low temperature.The effect of cooling technique on the physicochemical properties of the developed system was investigated.

Film coated floating tablets using sublimable substances

During the past few decades floating drug delivery systems(FDDSs)have been developed to prolong gastric retention time and obtain sufficient drug bioavailability[1].To avoid unpredictable time to float due to variable pH of the gastric fluid in each subject and food in the stomach[2],sublimation technique is the new interesting approach to prepare noneffervescent FDDSs[3].The objective of the present study was to develop the low-density film coated floating tablets using sublimable substances.

Preparation and physical properties of itraconazole-loaded nanoemulsions using pineapple starch as co-emulsifier

Pineapple plant(Ananascomosus L.Merr.)is a leading edible member of the Bromeliaceae family[1].Nanoemulsions containing itraconazole,a poorly water-soluble drug using pectin as a polymeric emulsifier,are currently under investigation[2].The physicochemical and rheological properties as well as structural characterizations of cassava and mungbean starches have been reported[3].However,the application of pineapple starch as co-emulsifier of pharmaceutical excipients for pharmaceutical industry has not been investigated.

Special issue: Pharmaceutical innovation

"Pharmaceutical innovation" is an interdisciplinary area of the pharmaceutical sciences including drug development with a focus on manufacturing, process control, and technology, among many other subfields of research. In this special issue, we have invited all participants attended the International Conference and Exhibition on Pharmaceutical Sciences and Technology 2018 under the theme of pharmaceutical innovation and translational research for human health, held in Bangkok during January 24–25, 2018, to submit the research papers and after peer-review process, 10 of them were selected.

Bioadhesiveness of thiolated pectin for buccal delivery of carbenoxolone sodium

Pectin is a biopolymer that has numerous useful purposes in food and beverage industry, cosmetic products and pharmaceutical fields. One of the important properties of pectin is its bioadhesive properties. Native pectin provides fair bioadhesive properties that can be improved by modification of pectin structure. The immobilization of thiol groups on polymer can significantly improve the bioadhesive properties due to in situ cross-linking between thiol groups of polymer and mucin [1].

Effect of solvent on properties of pectin microspheres prepared by emulsion-dehydration technique

In the controlled release area,biodegradable microspheres are one of the most helpful devices to deliver materials in an effective,prolonged and safe manner[1].Biodegradable pectin microspheres could provide an approach for developing controlled release drug delivery systems.Pectin is a naturally occurring,non-toxic,water-soluble polysaccharide used in many food industries.Pectin has increasingly gained acceptance as a carrier polymer for site-specific delivery and controlled release dosage forms,such as beads,pellets,tablets,and films[1,2].

Stability study of resveratrol-loaded emulsions using pectin as an emulsifier

Phenolic compound such as resveratrol has been suggested to prevent cancer and heart diseases because of its anti-oxidant and anti-inflammatory activities[1].However,therapeutic application of resveratrol is quite limited due to its poor solubility,low bioavailability,photosensitive and auto-oxidation properties[2].The aim of this study was to prepare resveratrolloaded emulsions using pectin as an emulsifier.The emulsions should be stable for up to 7 days,before further manufacturing processes.

Doxorubicin: The dogma and the bone

Doxorubicin is an anthracycline drug used as frontline chemotherapy of osteosarcoma among other types of cancers.While quite effective in providing a good control over the tumours in some patients,it can cause significant toxicity to organs such as the heart[1].Attempts to ameliorate this toxicity with agents such as dexrazoxane have been successful,but not without complications[2]as will be discussed in this talk.Pigment epithelium-derived factor(PEDF),a potent antiangiogenic and osteogenetic protein[3],was used to reduce this side-effect,together with an analysis of levels of adenosine triphosphate(ATP)and reactive oxygen species(ROS).The effects of low dose doxorubicin in a clinically relevant dosing model will be discussed.