Objective: The objective of this study is to enhance the solubility, dissolution and shelf-life of bosentan by formulating it as S-SMEDDS capsules.
Materials and methods: Solubility of bosentan was tested in various liquid vehicles such as oils (rice bran and sunflower), surfactants (span 20 and tween 80) and co-surfactants (PEG 400 and propylene glycol) and microemulsions were developed. Bosentan was incorporated into appropriate microemulsion systems which were previously identified from pseudo ternary phase diagrams. Bosentan-loaded SMEDDS were evaluated for drug content, drug release, zeta potential, and droplet size. The selected liquid SMEDDS were converted into solid SMEDDS by employing adsorption and melt granulation. Solid SMEDDS were characterized for micromeritics and evaluated for drug content, drug release, and shelf-life.
Results: Isotropic systems R5, R13, S5, and S13 with submicron droplet size had exhibited 85.45, 94.12, 81.67, and 96.64% drug release, respectively. Solid SMEDDS of MR13 and AS13 formulations with rapid reconstitution ability, exhibited 84.85 and 86.74% of on par drug release. The formulations were physicochemically intact for 1.02 and 1.56 years.
Discussion: Liquid SMEDDS composed with PEG400 had displayed optimal characters. Solid SMEDDS had high-dissolution profiles than bosentan due to modification in the crystalline structure of drug upon microemulsification.
Conclusion: Thus, solid SMEDDS addressed the solubility, dissolution, and stability issues of bosentan and becomes an alternate for clinical convenience. 相似文献
Significance: Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia.
Methods: Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers.
Results: Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product.
Conclusion: Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems. 相似文献
Materials and methods: The critical micelle concentration (CMC) of surfactants, including sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), dodecyl trimethyl ammonium bromide (DTAB), cetyltrimethyl ammonium bromide (CTAB) and polysorbate (Tween-20 and Tween-80), was obtained using the platinum ring method. Contact angles of surfactant solutions on the excipient compacts and double-distilled water on the mixture of surfactant and the other excipient (magnesium stearate (MgSt) or sodium alginate (SA)) were measured by the sessile drop technique. Besides, surface free energy of excipients was calculated by the Owens method. Finally, the disintegration of tablets and in vitro dissolution testing were performed according to the method described in USP.
Results and discussion: The wettability of excipients could be enhanced to different extent with low concentration of surfactant solutions and maintained stable basically after CMC. For MgSt (hydrophobic excipient), the shorter the hydrophobic chain (C12, including SDS and DTAB), the better the wettability with the addition of surfactant in the formulation, leading to the shorter disintegration time of tablets and higher drug release rate. In contrast, the wettability of SA (hydrophilic excipient) was reduced by adding surfactant, resulting in the longer disintegration time of tablets and lower release rate.
Conclusion: The modulation of the wetting of pharmaceutical excipients by surfactant had changed the disintegration time of tablets and drug release rate to a greater extent. 相似文献
Objective: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.
Materials and methods: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.
Results: LSH tablets exhibited dynamic swelling–deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.
Discussion: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.
Conclusions: These finding indicates that LSH holds potential to be developed as sustained release material for tablet. 相似文献
Significance: These observations of cocrystal stability under various conditions are useful coformer criteria when cocrystals are selected as the active pharmaceutical ingredient in drug development.
Method: The relative stability was determined from the preferentially formed cocrystals under various conditions.
Result: Cocrystal of APAP–OXA was more stable than that of APAP–MLA in a ternary cogrinding system and possessed thermodynamical stability. On the other hand, when grinding with moisture or maintaining at high temperatures and relative humidity conditions, APAP–MLA was more stable, and OXA converted to OXA dihydrate. In the slurry method, APAP–OXA was more stable in aprotic solvents because the APAP–OXA with low-solubility product precipitated.
Conclusions: The relative stability order was affected by preparing conditions of presence of moisture. This order might attribute to the small difference of crystal structure in the extension of the hydrogen bond network. 相似文献
Significance: A simplified scoring system for the biopharmaceutics risk assessment roadmap (BioRAM) is proposed to guide product development.
Methods: Factorial design of experiments was employed to study the effect of formulation and process variables on CQA’s. The in vivo model was developed for predicting the fraction of drug absorbed and to identify the effect of formulation components on drug absorption.
Results: BioRAM yielded low scores for fluconazole absorption with respect to severity (risks of sub and supra-bioavailable drug products), probability of incidence of bioinequivalent results and capacity of detection. The results demonstrated that dissolution was highly influenced by the active pharmaceutical ingredient (API) polymorphism and the ratio of diluents. Process variables (mixing time, lubricant concentration, lubrication time and filling speed) did not impact the clinical outcome of the formulation with respect to dissolution and content uniformity.
Conclusions: Understanding the clinical implications of the adopted formulation approach led to the construction of purposeful design space and control strategy. 相似文献
Objective: The aim of this study is to construct novel NLCs as nanocarriers for co-delivery of doxorubicin (DOX) and cisplatin (CDDP) to treat breast cancer.
Methods: DOX and CDDP loaded NLCs (D–C-NLCs) were prepared by the solvent diffusion method. The in vitro cytotoxicity and synergistic studies of different formulations were evaluated on human breast cancer cells (doxorubicin resistant) (MCF-7/ADR cells). In vivo anti-tumor effects were observed on the murine bearing MCF-7/ADR cells model.
Results: D–C-NLCs showed the highest cytotoxicity and synergistic effect of two drugs in tumor cells in vitro. The in vivo study revealed the greatest anti-tumor activity than the other formulations in the breast cancer model.
Conclusion: The constructed NLCs could be used as a novel carrier for co-delivery of DOX and CDDP for breast cancer therapy. D–C-NLCs could be a promising targeted and combinational therapy nanomedicine. 相似文献
Objective: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC).
Materials and methods: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical–physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model.
Results and discussion: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo.
Conclusion: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC. 相似文献
Objective: This work is directed toward masking the bitter taste of ondansetron HCl (ONS) utilizing the excipient, which can delay the reach of drug to the taste buds.
Material and methods: Magnesium aluminum silicate (Veegum F), a clay material having capability to adsorb the drugs onto it, was used. The adsorption systems of ONS with Veegum were obtained by dynamic adsorption technique and examined by scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) for morphology, thermal behavior, and interactions. The taste assessment of prepared systems was done by in vitro method based on drug release.
Results: The molecular interaction between ONS and Veegum in the system was revealed by FTIR spectroscopy. A change in thermal behavior of the system was observed owing to interaction or replacement of the cationic groups of Veegum with that of ONS. XRD studies revealed that the prepared system was having lower crystallinity as compared to ONS. The in vitro drug release study showed that ONS release from the system was relatively slow in basic environment than the acidic one.
Discussion: Adsorption of ONS on the surface of Veegum was mainly due to electrostatic interactions and hydrogen bonding.
Conclusion: The experimental results reveal the successful intercalation of ONS into the space available between the layers of Veegum. Furthermore, this resulted in a control on drug release in salivary pH resulting in a concentration lower than bitterness threshold. 相似文献
Highlights
(1) The interfacial durability of CNT/PVDF nanofibers was enhanced to increase contact area by reinforcing CNT.
(2) The efficiency of CNT/PVDF actuators was improved due to interfacial properties.
(3) Thin thickness drum-type collector was made to enhance nanofiber alignment.
(4) The arranged CNT/PVDF nanofibers exhibited better mechanical and actuating displacements. 相似文献
Significance: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative.
Methods: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS).
Results: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells.
Conclusions: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use. 相似文献
Significance: Gambogic acid (GA) can inhibit the growth of various cancer cells. However, the short elimination half-life time and treatment without targeting limits its application. OACS was synthesized as delivery carrier for GA by us, but the deeper characterization of OACS, such as molecular modeling, pharmacokinetics, and biodistribution were not investigated.
Methods: Gambogic acid loaded OACS micelles (GA–OACS) were evaluated by the molecular modeling, characterized by TEM, DLS, IR, 1HNMR, XRD. Confocal laser scanning microscope and flow cytometry were analyzed for cell uptake study. Imaging analysis was used to show the distribution of OACS in vivo directly, pharmacokinetics and biodistribution were also investigated.
Results: The molecular modeling result showed that GA could encapsulated stably in the core of OACS micelles. TEM, IR, 1HNMR, and XRD also suggested that GA was encapsulated in amorphous form in the core of OACS micelles. AUC and elimination half-life of GA–OACS were all increased by 1.5-fold and 2.0-fold compared with GA–ARG in rat, respectively. Biodistribution study indicated that GA–OACS was distributed mainly in the liver. GA amount in the kidney and heart was greatly reduced in the GA–OACS group. From the imaging analysis, OACS distribution in the liver was the most.
Conclusions: OACS was an excellent carrier for GA intravenous delivery to prolong half-life. Moreover, OACS targeted on liver. 相似文献
Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine.
Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling.
Results: According to the in vitro results, the selected SMEDDS consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%).
Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms. 相似文献
Significance: This strategy provides simple technique for dissolution enhancement of slowly dissolving drugs with high scaling up potential.
Methods: Aerosil was dispersed in ethanolic solution of flurbiprofen in the presence and absence of hydrophilic polymers. Acidified water was added as antisolvent to produce controlled precipitation. The resultant particles were centrifuged and dried at ambient temperature before monitoring the dissolution pattern. The particles were also subjected to FTIR spectroscopic, X-ray diffraction and thermal analyses.
Results: The FTIR spectroscopy excluded any interaction between flurbiprofen and excipients. The thermal analysis reflected possible change in the crystalline structure and or crystal size of the drug after controlled precipitation in the presence of hydrophilic polymers. This was further confirmed by X-ray diffraction. The modulation in the crystalline structure and size was associated with a significant enhancement in the dissolution rate of flurbiprofen. Optimum formulations were successfully formulated as rapidly disintegrating tablet with subsequent fast dissolution.
Conclusions: Precipitation on a large solid surface area is a promising strategy for enhanced dissolution rate with the presence of hydrophilic polymers during precipitation process improving the efficiency. 相似文献
Objective: The aim of this work was to design and characterize liposomal vesicles as drug delivery systems for the LR peptide, evaluating the possible benefits of the pH-responsive feature in improving intracellular delivery.
Materials and methods: For this purpose, conventional and pH-sensitive liposomes were formulated, compared regarding their physical-chemical properties (size, PDI, morphology, in vitro stability and drug release) and studied for in vitro cytotoxicity against a cDDP-resistant cancer cells.
Results and discussion: Results indicated that LR peptide was successfully encapsulated in both liposomal formulations but at short incubation time only LR loaded pH-sensitive liposomes showed cell inhibition activity while for long incubation time the two kinds of liposomes demonstrated the same efficacy.
Conclusions: Data provide evidence that acidic pH-triggered liposomal delivery is able to significantly reduce the time required by the systems to deliver the drug to the cells without inducing an enhancement of the efficacy of the drug. 相似文献
Objective: The present study aimed at improving the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media.
Methods: The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised intestinal segments. Receiver media that establish sink conditions were investigated for their foaming potential and toxicity. Dissolution/permeation experiments with the optimized conditions were then tested for two particle sizes of the BCS class II drug aprepitant.
Results: Fa/FeSSIFmod were toxic for excised rat ileal sheets but not duodenal sheets, the compatibility with jejunal segments depended on the bile salt concentration. A non-foaming receiver medium containing bovine serum albumin (BSA) and Antifoam B was nontoxic. With these conditions, the permeation of nanosized aprepitant was higher than of the unmilled drug formulations.
Discussion: The compatibility of Fa/FeSSIFmod depends on the excised intestinal region. The chosen conditions enable dissolution/permeation experiments with excised rat duodenal segments. The experiments correctly predicted the superior permeation of nanosized over unmilled aprepitant that is observed in vivo.
Conclusion: The optimized setup uses FaSSIFmod as donor medium, excised rat duodenal sheets as permeation membrane and a receiver medium containing BSA and Antifoam B. 相似文献
Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy.
Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption.
Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation.
Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis. 相似文献
Objective: The objective of the present work was to prepare ibuprofen-loaded DCP particles and further to analyze them for compressibility and dissolution behavior.
Materials and methods: Various crystallization techniques such as solvent evaporation (SE), melt crystallization (MC), melt sonocrystallization (MSC), antisolvent crystallization (AC), and antisolvent sonocrystallization (ASC) were screened for the preparation of ibuprofen-loaded DCP. Products obtained from different techniques were analyzed for physicochemical, micromeritic and compression properties.
Results and discussion: ASC technique was found to be suitable for preparing directly compressible ibuprofen-loaded DCP particles. The change in the crystal habit (needle to plate shape) of ibuprofen and its crystallization in miniscular form onto the surface of DCP particles showed significant improvement in the dissolution rate and compression properties of ibuprofen due to an increase in specific surface area when compared with ibuprofen crystallized by other techniques. Additionally, the tablets prepared from ASC powder did not require binder since ibuprofen acted as melt binder during compression.
Conclusion: Directly compressible ibuprofen-loaded DCP particles can serve as an alternative for conventional ibuprofen tablets prepared by wet granulation technique. 相似文献
Methods: Multicomponent crystals were prepared by solvent evaporation method, kneading, and combining mechanical and thermal activation. DSC, FT-IR spectroscopy, X-ray diffraction, SEM-EDS, and SSNMR were used to investigate their formation. Measurements of solubility and dissolution rate were carried out for the pharmaceutical characterization.
Results: The formation of multicomponent crystals of gliclazide and tromethamine was confirmed by all the techniques. In particular, FT-IR and NMR measurements revealed that the interaction between drug and coformer leads to significant changes of the hydrogen bond scheme, and that almost all the functional groups of the two molecules are involved. The dissolution profile of the new phase is significantly better than that of both pure gliclazide and of the reference commercial product Diabrezide®.
Conclusions: The new system shows an improved pharmaceutical behavior and could be formulated in a dosage form to obtain a rapid and complete release of the drug available for absorption. 相似文献