Search

The lack of trypsin in the intestines may end up with malnutrition; thus, trypsin replacement therapy is required in such cases. The main objective of this study is to formulate and evaluate polymeric nanocapsule (PNC) systems able to deliver trypsin to the small intestines with the minimal release in the stomach with the maximum biological activity. Four nanocapsule formulations were prepared by double emulsion/evaporation method as w/o/w and s/o/w. Particle size, encapsulation efficiencies, drug release in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF), morphology, the biological activity of encapsulated trypsin and shelf-life stability were investigated for all formulations. All formulations had a spherical shape with submicron size, and encapsulation efficiency more than 80%. The biological activity of encapsulated trypsin was significantly affected by the amount of trehalose and whether the formulations were prepared as s/o/w or w/o/w (P < 0.05). Most of the encapsulated protein was released sustainedly at the target site (SIF) over 24 h with minimum amount release in the gastric fluids. Also, more than 90% of physical integrity trypsin encapsulated in all formulations was retained after storage under chilled conditions for six months. However, the enzymatic assay results show that with low trehalose content, the biological activity was low, while increasing the trehalose amount increased the shelf stability to reach around 100% after six months of the study. The results obtained in this research work clearly indicated a promising potential of controlled release polymeric nanocapsules containing trypsin to target the small intestine and protect trypsin from the harsh condition facing the proteins during the process of preparation or the period of storage.

The aim of this work is to enhance the dissolution of furosemide, a hydrophobic drug used in treating hypertension. Solid dispersion via lyophilisation was employed for this purpose. Sugar and oligosaccharide, trehalose and hydroxyl propyl-γ-cyclodextrin (HP-γ-CD), were used as carrier molecules. Complexation of drug molecules with cyclodextrins changes its physical properties, including solubility. Trehalose was selected as it is a hydrophilic molecule as well as it reduces the cellular oxidative stress. Binary solid dispersions at three weight ratios drug to sugar/oligosaccharide were prepared. Solid dispersions were compared with unprocessed drug molecules and the marketed product. Samples were characterized via Fourier transform infrared spectroscopy, differential scanning calorimetry and In vitro drug dissolution. All lyophilized samples showed a significant improvement (p < 0.05) in furosemide dissolution in the aqueous dissolution medium. The study introduces furosemide/HP-γ-CD and furosemide/trehalose freeze dried composites as potential candidate powders to formulate for example fast disintegrating tablets.

Background: Albumin-based nanoparticles have been used as drug carriers to improve therapeutic effect. This study aimed to produce sulfasalazine (SSZ)-loaded bovine serum albumin (BSA) nanoparticles by desolvation technique and characterize their physical properties. Drug loading effect was also investigated.\ud \ud Methods: SSZ albumin nanoparticles were batch produced by desolvation technique and lyophilized. Physical characteristics of nanoparticles including size distribution, zeta potential and entrapment efficiency were studied.\ud \ud Results: Nanoparticles were spherical and typically 200–400 nm with low polydispersity (PDI). The zeta potentials of nanoparticles ranged from −21 to −41 mV, which were attributed to BSA and SSZ. The highest actual drug loading was close to 0.5%w/w. The addition of 2% sucrose during lyophilization was essential to avoid cake collapse and the particle sizes increased slightly where their PDI values were low. Although the presence of sucrose led to a slight reduction in zeta potential, it had limited effect on zeta potential of the nanoparticles. The interactions between SSZ and formulation excipients were also confirmed with FTIR and DSC analyses.\ud \ud Conclusion: Desolvation technique produced stable sulfasalazine-loaded nanoparticles that can be administered parenterally.\ud \ud KEYWORDS: sulfasalazine; nanoparticle; albumin; physical property

Niosomes are colloidal vesicles that capable of encapsulating drugs as a carrier for drug delivery system. They are formed by self-assembly of a non-ionic surfactant with cholesterol and co-surfactant. In this work, cinnarizine-containing niosomes comprised of sorbitan monostearate (Span® 60), cholesterol and co-surfactant (Cremophor® ELP, Cremophor® RH40 or Solutol® HS15) were prepared using conventional thin film hydration and microfluidic methods. Effects on characteristics of niosomes with the presence of poorly water-soluble drug, cinnarizine in the niosomal formulations prepared using different methods and incorporation of different co-surfactants were studied and compared for their particle size, polydispersity index (PDI) and encapsulation efficiency. Dynamic light scattering was employed for particle size measurements and drug loading studies were analysed using high performance liquid chromatography (HPLC). The morphology of niosomes was characterized using optical light microscopy.

Novel niosomal formulations containing cinnarizine were developed to enhance its drug characteristics. In this work, niosomes (non-ionic surfactant vesicles) were prepared by conventional thin-film hydration (TFH) and microfluidic (MF) methods with sorbitan monostearate (Span&reg, 60), cholesterol, and co-surfactants (Cremophor&reg, ELP, Cremophor&reg, RH40 and Solutol&reg, HS15) as key excipients. The aim was to study the effect of cinnarizine on the characteristics of different niosomal formulations manufactured by using different methods. For effective targeted oral drug delivery, the efficacy of niosomes for therapeutic applications is correlated to their physiochemical properties. Niosome vesicles prepared were characterised using dynamic light scattering technique and the morphology of niosomes dispersion was characterised using optical microscopy. Dialysis was carried out to purify niosome suspensions to determine drug loading and drug release studies was performed to study the potential use of niosomal systems for cinnarizine.

Clinical applications of oral protein therapy for the treatment of various chronic diseases are limited due to the harsh conditions encounter the proteins during their journey in the Gastrointestinal Tract. Although nanotechnology forms a platform for the development of oral protein formulations, obtaining physiochemically stable formulations able to deliver active proteins is still challenging because of harsh preparation conditions. This study proposes the use of poly (D, L-lactic-co-caprolactone)-based polymeric nanocapsules at different monomers’ ratios for protein loading and oral delivery. All formulations had a spherical shape and nano-scale size, and lysozyme encapsulation efficiency reached 80% and significantly affected by monomers’ ratio. Trehalose and physical state of lysozyme had a significant effect on its biological activity (P

PURPOSE:\ud Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug.\ud \ud METHODS:\ud In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy.\ud \ud RESULTS:\ud The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min.\ud \ud CONCLUSIONS:\ud the physical mixing and freeze drying processes significantly increased the percentage of drug release with time.

Proteins can be encapsulated in niosomes as they are known to protect proteins against the surrounding env ironment. Niosomes of Span™ 65/cholesterol/pluronic ® F -127 were prepared by thin film hydration method. Insulin and lysozyme were chosen as model proteins. Niosomes were chara c-terised for morphology by Transmission Electron M icroscopy (TEM) and vesicles size using Dynamic Light Scattering. The entrapment efficiency of protein in niosomes was determined by complete vesi-cle disruption using 50:50% isopropanol:buf fer, followed by analysis of the resulting so lutions by HPLC method. Thermal behaviour of the niosomes was investigated using Differential Scanning Calo-rimetry (DSC). Protection of proteins against simulated gastric fluid (SGF) and simu lated intestinal fluid (SIF) were also assessed. The results showed that niosomes prepared with diffe r ent molar ratios % of Span™ 65, cholesterol and pluronic ® F -127 successfully produced with insulin and lysozyme. For insulin co n taining niosomes, the ratio % of 64.7 (Span™ 65): 32.3 (cholesterol): 3.0 (pluronic ® F - 127) produced the highest protein encapsulation eff i-ciency and the smallest vesicle size of 653.6 nm. For lysozyme containing niosomes, the maximum pr o tein encapsulation was found in 72.75/24.25/3.00% molar ratio of Span™ 65/cholesterol/pluronic ® F -127 niosomes with vesi cle size of 627.3 nm. The release study of proteins from the niosomal preparations in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) revealed that insulin and lysozyme efflux from the niosomes is a biphasic process. The results indicate that Span™ 65 niosomes could be developed as controlled release dosage forms for delivery of peptides and proteins such as insulin and lysozyme.

Silicified microcrystalline cellulose pellets with hydroxypropyl methylcellullose (HPMC) as modifier were prepared using a\ud mixed solvent as liquid binder. Pellets were produced using extrusion-spheronization with a mixed solvent consisting of water and isopropanol\ud as liquid binder. The key spheronization aid was Prosolv® SMCC 90. Low viscosity grade HPMC was incorporated aiming to\ud modify release of indometacin. Physical characteristics including breaking load, apparent density and flow properties, particle size distribution\ud and shape were determined. Drug loaded pellets were also tested for dissolution profiles. By adjusting liquid binder property, at\ud isopropanol to water ratio of 3.5 to 6.5, pellets of desirable size and shape with reasonable yields were obtained. Pellets exhibited good\ud flow property and they were mechanically strong. Pellet with higher HPMC content displayed a faster drug dissolution profile. This was\ud because low viscosity grade HPMC was not enough to create strong gel. Instead hydration of HPMC molecules increased matrix’s\ud hydrophilicity and weakened the structure of pellet faster. The release of indometacin was partly based on the erosion of hydrated\ud matrix. The presence of HPMC in the pellets would require a mixed solvent to produce desirable shape. Incorporation of HPMC had\ud modified drug release from the pellets without further coating. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47924.

This work aimed to investigate and optimise the effects of co-surfactants, hydration volume, and time on the entrapment of methylene blue (MB) within niosomes and the vesicle sizes of MB-loaded niosomes upon different storage temperatures. Niosomes were prepared by the thin film hydration method followed by gel permeation chromatography to obtain purified niosome suspensions. The probe sonication method was used to reduce the niosome vesicle size and distribution. Highest entrapment efficiencies (%EE) were determined for niosomal formulations containing Span® 60, cholesterol, and Cremophor® ELP (E2 and E3), which were prepared with a hydration volume of 5 mL. The hydration time was 15 min for E2 and 60 min for E3 (%EE = 40.1 ± 7.9% and 32.9 ± 10.1% for E3 and E2, respectively). The final lipid contents in the formulations were shown to have an impact on %EE.

Silicified microcrystalline cellulose (SMCC), Prosolv SMCC 50 was used as spheronization aid to manufacture pellets by extrusion and spheronization. Different ratios of SMCC to lactose were used to manufacture pellets using appropriate levels of water as liquid binder. Avicel PH101 based pellets were also manufactured for comparison of their physical properties. The ratio of liquid binder to spheronization aid was critical to produce pellets of desired size and shape. Extrudates composed of 20% aid could withstand only smaller spheronization force in order to be shaped into pellets. The successful products fulfilled the quality of pellets such as narrow size distribution and spherical in shape. The highest surface tensile strength was observed in pellets with equal ratio of lactose to SMCC while pellets having 20% aid disintegrated rapidly within 15 min. Furthermore, Prosolv SMCC 50 based pellets possessed a stronger surface tensile strength when compared with Avicel PH101 based pellets. In conclusion, Prosolv SMCC 50 has showed to be a good spheronization aid for extrusion and spheronization when used in the range of 20 to 80% content. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43829.

Xanthan gum (XG), a hydrophilic biopolymer with modified release properties, was used to produce directly compressed matrix tablets containing a model drug, sodium p-aminosalicylate. Three formulations were prepared, each containing a different calcium dihydrate salt: calcium chloride, calcium sulfate or dibasic calcium phosphate. The aim of the investigation was to relate the calcium ion content and solubility of the calcium salt to the in vitro drug release profile of the xanthan matrices. Tablet hydration, erosion and drug release were determined in distilled water using the British Pharmacopoeia (BP) paddle method. The data showed that the overall drug release was the greatest with addition of calcium sulfate, followed by calcium chloride and dibasic calcium phosphate. The chloride salt formulation displayed the greatest percentage erosion due to rapid mass loss during the initial phase, followed by those with sulfate or phosphate salts. As xanthan gel viscosity increased and drug release was also found to be lower, it can be concluded that drug release is influenced by the solubility of the salt present in the formulation, since these parameters determine the viscosity and structure of the gel layer.