Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Context: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.

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.     

SeDeM expert system a new innovator tool to develop pharmaceutical forms

Context: The SeDeM expert system is based on the experimental study and quantitative determination of the characterization parameters of powdered substances, the aim being to determine whether a substance is suitable for producing tablets by means of direct compression (DC) technology, thereby reducing the lead time for pre-formulation studies. Additionally, this expert system also provides formulations with a minimum number of excipients.

Objective: We used this system to analyze suitable formulas for the production of orodispersible ibuprofen tablets.

Method: Twenty-one disintegrants and ibuprophen were characterized using SeDeM methodology.

Results: The results indicated that production of ibuprofen tablets by DC would require improvements in the dimension and compressibility factors of the active pharmaceutical ingredient. The expert system analysis provided the specific percentage of disintegrant needed to blend with ibuprofen and a standardized formula of lubricants in order to obtain a powder mix that would successfully produce tablets by DC. The eight formulas proposed by SeDeM were produced and tested in the laboratory.

Conclusion: All eight formulas successfully produced tablets by DC, but only four of them could be considered suitable for use as an orodispersible tablet and accomplishes all the pharmaceutical quality parameters. So, in fact, the use of the SeDeM system reduced the time of medicine’s development and therefore the cost of the activity.     

Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials and methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet.

Results: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol.

Discussion: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets.

Conclusion: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.     

RGD peptide targeted lipid-coated nanoparticles for combinatorial delivery of sorafenib and quercetin against hepatocellular carcinoma

Context: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics.

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.     

Controlled precipitation for enhanced dissolution rate of flurbiprofen: development of rapidly disintegrating tablets

Objective: The aim of this work was to investigate the potential of controlled precipitation of flurbiprofen on solid surface, in the presence or absence of hydrophilic polymers, as a tool for enhanced dissolution rate of the drug. The work was extended to develop rapidly disintegrated tablets.

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.     

Applying the approximation method PAINT and the interactive method NIMBUS to the multiobjective optimization of operating a wastewater treatment plant

Using an interactive multiobjective optimization method called NIMBUS and an approximation method called PAINT, preferable solutions to a five-objective problem of operating a wastewater treatment plant are found. The decision maker giving preference information is an expert in wastewater treatment plant design at the engineering company Pöyry Finland Ltd. The wastewater treatment problem is computationally expensive and requires running a simulator to evaluate the values of the objective functions. This often leads to problems with interactive methods as the decision maker may get frustrated while waiting for new solutions to be computed. Thus, a newly developed PAINT method is used to speed up the iterations of the NIMBUS method. The PAINT method interpolates between a given set of Pareto optimal outcomes and constructs a computationally inexpensive mixed integer linear surrogate problem for the original wastewater treatment problem. With the mixed integer surrogate problem, the time required from the decision maker is comparatively short. In addition, a new IND-NIMBUS^® PAINT module is developed to allow the smooth interoperability of the NIMBUS method and the PAINT method.     

Development of optimized self-nanoemulsifying lyophilized tablets (SNELTs) to improve finasteride clinical pharmacokinetic behavior

Objective: Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS).

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.     

Enhancing the solubility and masking the bitter taste of propiverine using crystalline complex formation

Context: Patient compliance can be reduced when bitter-tasting compounds, such as propiverine hydrochloride, are administered orally. Propiverine hydrochloride is an example of a drug with a bitter taste, used for the treatment of overactive bladders.

Objective: This study tested whether propiverine free base palatability and aqueous solubility could be improved by crystalline complex formation.

Materials and methods: We used 42 compounds, and found 9 new propiverine crystalline complexes. The properties and solubility of these complexes were studied using a range of techniques. A taste perception study was carried out using a taste sensor to evaluate the taste masking ability of the crystalline complex formation.

Results: The melting points of the crystalline complexes were higher than that of propiverine. The dissolution rates of the crystalline complexes in aqueous buffer solution (pH 6.8) and in purified water were much faster than that of propiverine. Propiverine salicylic acid crystalline complex had substantially less bitterness than propiverine hydrochloride, which was extremely bitter.

Discussion: The present findings indicated that crystalline complex formation provided an effective approach to enhancing propiverine solubility, and to masking its bitter taste.

Conclusion: Crystalline complex formation represents a useful and valuable technique for the preparation of orally disintegrating tablets and improving patient compliance, even for substances with bitter tastes.     

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery

Context: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on.

Objective: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers.

Methods: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. ¹H nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates.

Results and discussion: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ～12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX.

Conclusion: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.     

Development of a Raman method to follow the evolution of coating thickness of pellets

Context: Although several methods have been investigated to measure the film thickness of tablets and its correlation with the dissolution behavior, much fewer such investigations exist for pharmaceutical pellets.

Objective: To study the possibility of measuring the film thickness and predicting the dissolution behavior of pellets produced in different fluid bed equipments with Raman spectroscopy.

Materials and methods: Pyridoxine hydrochloride-layered pellets were produced and coated in two different Strea-1 equipments. Raman spectra were collected and analysed to set up a calibration model based on the film thickness data calculated from Camsizer analysis results. Dissolution tests were done according to Ph. Eur. standards.

Results: Raman spectroscopy proved to be a good tool in the measurement of film thickness. Polymer weight gain showed a linear correlation with film thickness but was a poor predictor of dissolution results below a threshold value.

Conclusion: The Raman spectroscopic measurement of a small sample can provide accurate data of the film thickness. The investigation suggests that a threshold value might exist for the film thickness above which it can be used to judge future dissolution results.     

In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems

Objective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach.

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.     

Processing of pharmaceutical materials by electrospraying under reduced pressure

Context: Electrospraying was used in drug particle production.

Objective: The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied.

Materials and methods: A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed.

Results: The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure.

Discussion and conclusions: A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.     

Investigations on the transfer of porphyrin from o/w emulsion droplets to liposomes with two different methods

Context: Due to their small particle size, colloidal fat emulsions are suitable for intravenous administration. In order to obtain information on their potential in vivo performance, it is important to find a simple and effective in vitro assay to evaluate the drug release behavior of such particles.

Objective: Two in vitro methods were studied to measure the transfer of a lipophilic model drug from colloidal o/w emulsion droplets (donor) to liposomes (acceptor), which serve as model membranes mimicking cell membranes in the body. In the first method (column method) the acceptor particles were neutral unilamellar vesicles. In the second method (MLV method), multilamellar vesicles (MLV) were used as acceptor.

Materials and methods: The donor nanoemulsions were prepared by high pressure homogenization. Z-average particle size, polydispersity index and zeta potential were determined.

Results: The transfer of porphyrin was moderate to the acceptor MLV and rapid to the acceptor unilamellar vesicles. The amount of transferred porphyrin at the end of the experiment depended on the transfer method and the donor/acceptor ratio. With both acceptors the transfer of porphyrin stopped at a concentration lower than the theoretical equilibrium values.

Discussion: Many factors such as acceptor particle size and donor to acceptor lipid molar ratio affect the drug transfer from the donor particles to the different acceptors.

Conclusion: Both methods seem to be suitable to study the drug transfer from such colloidal emulsion and the use of lipophilic acceptor particles is a better approach to the conditions in blood.     

New nanomicelle curcumin formulation for ocular delivery: improved stability,solubility, and ocular anti-inflammatory treatment

Context: A stable topical ophthalmic curcumin formulation with high solubility, stability, and efficacy is needed for pharmaceutical use in clinics.

Objectives: The objective of this article was to describe a novel curcumin containing a nanomicelle formulation using a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (PVCL–PVA–PEG) graft copolymer.

Methods: Nanomicelle curcumin was formulated and optimized and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vitro cellular uptake/in vivo corneal permeation, and in vitro antioxidant activity/in vivo anti-inflammatory efficacy.

Results: The solubility, chemical stability, and antioxidant activity were greatly improved after the encapsulation of the PVCL–PVA–PEG nanomicelles. The nanomicelle curcumin ophthalmic solution was simple to prepare and the nanomicelles are stable to the storage conditions, and it had good cellular tolerance. Nanomicelle curcumin also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake and in vivo corneal permeation as well as improved anti-inflammatory efficacy when compared with a free curcumin solution.

Conclusions: These findings indicate that nanomicelles could be promising topical delivery systems for the ocular administration of curcumin.     

To enhance the efficiency of nefopam transdermal iontophoresis by using a novel method based on ion-exchange fiber

Background: In the system of the iontophoresis, the external electric field made the ions in the system moving directly, then, the current was generated. Because the current was contributed by all ions in the system, and the small ions with large amount often had higher conductibility than the drug ions, the fraction of the total current contributed by the drug ions was often low. It was the main reason for the generally low efficiency of the transdermal iontophoretic drug delivery.

Objectives: The objective of this study was to find a novel method to increase the fraction of the total current contributed by the drug ions so as to enhance the drug's iontophoretic delivery.

Method: Iontophoretic transport of nefopam hydrochloride solution and iontophoretic transport of nefopam assisted by ion-exchange materials, including ion-exchange resin, ion-exchange membrane and ion-exchange fiber, across the rat skin were investigated.

Results: Both in vitro and in vivo iontophoretic transport experiments showed that the efficiency of the nefopam-fiber iontophoretic system for nefopam permeating across rat skin was the highest among four iontophoretic systems (nefopam solution, nefopam-resin, nefopam-membrane and nefopam-fiber).

Conclusion: The results of this study suggested that there was an enhancement of nefopam across rat skin by ion-exchange fibers in ion-exchange fibers assisted iontophoresis. The present study has demonstrated the potential of a new approach of using ion-exchange fibers to improve the efficiency of the transdermal iontophoresis for cationizable drugs.     

Determining osmotic pressure of drug solutions by air humidity in equilibrium method

Objective: To establish a new osmotic pressure measuring method with a wide measuring range.

Method: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution. The freezing point osmometry is used as a control.

Results: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method.

Conclusion: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.     

Budesonide/cyclodextrin complex-loaded lyophilized microparticles for intranasal application

Objective: Lyophilized microparticles composed of budesonide (BDS), hydroxypropyl-β-cyclodextrin (HP-β-CD), and hydroxypropylmethylcellulose (HPMC) or sodium carboxymethylcellulose (CMC-Na) were developed for intranasal delivery and their characteristics were evaluated.

Materials and methods: The particle size and morphology were assessed by mean diameter measurement and scanning electron microscopy (SEM) image, respectively. The solid-state of products was tested by X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In vitro drug release and cytotoxicity to the primary human nasal epithelial (HNE) cells were also evaluated.

Results and discussion: Lyophilized microparticles exhibited vanishment of crystallinity of drug in XRPD analysis, the enfeeblement of carbonyl (C=O) stretching bands of carboxyl group in BDS in FT-IR spectra and the disappearance of endothermic peak of drug in the results of DSC study. Based on the results of solid-state studies, BDS was existed as an amorphous form in the lyophilized microparticles. CD complexation enhanced drug solubility and release rate, and HPMC or CMC-Na also improved drug dissolution rates. Cytotoxicity of developed microparticles to the HNE cells was measured and their safety to HNE cell was identified.

Conclusion: Developed microparticles can efficiently deliver insoluble drug, such as BDS, to the nasal epithelium and thus it may improve therapeutic efficacy in the respiratory tract.     

The influence of direct compression powder blend transfer method from the container to the tablet press on product critical quality attributes: a case study

Objective: The aim of this article is to compare the gravitational powder blend loading method to the tablet press and manual loading in terms of their influence on tablets’ critical quality attributes (CQA).

Significance: The results of the study can be of practical relevance to the pharmaceutical industry in the area of direct compression of low-dose formulations, which could be prone to content uniformity (CU) issues.

Methods: In the preliminary study, particle size distribution (PSD) and surface energy of raw materials were determined using laser diffraction method and inverse gas chromatography, respectively. For trials purpose, a formulation containing two pharmaceutical ingredients (APIs) was used. Tablet samples were collected during the compression progress to analyze their CQAs, namely assay and CU.

Results: Results obtained during trials indicate that tested direct compression powder blend is sensitive to applied powder handling method. Mild increase in both APIs content was observed during manual scooping. Gravitational approach (based on discharge into the drum) resulted in a decrease in CU, which is connected to a more pronounced assay increase at the end of tableting than in the case of manual loading.

Conclusions: The correct design of blend transfer over single unit processes is an important issue and should be investigated during the development phase since it may influence the final product CQAs. The manual scooping method, although simplistic, can be a temporary solution to improve the results of API’s content and uniformity when compared to industrial gravitational transfer.     

Design of polymeric nanoparticles and its applications as drug delivery systems for acne treatment

Objective: The aim of this study was to evaluate a formulation made of poly(lactide-co-glycolide) (PLGA) nanoparticles containing azelaic acid for potential acne treatment.

Methods: Azelaic acid-loaded PLGA nanoparticles were prepared by spontaneous emulsification processes using poloxamer 188 as stabilizer. Several manufacturing parameters such as stirring rate, concentration of stabilizer and different recovery methods were investigated. Nanoparticles were evaluated in terms of size, zeta potential, encapsulation efficiency, release kinetics and permeation kinetics in vitro. Furthermore, in vitro toxicological studies were performed in Saccharomyces cerevisiae model.

Results: The results showed that by adjusting some formulation conditions it was possible to obtain nanoparticles with high loading and a controlled drug release. Freeze-dried recovery altered the nanoparticles structure by enhancing porous structures and mannitol was required to control the mean particle size. The centrifugation recovery was found to be the best approach to nanoparticles recovery. Similar toxicity profiles were observed for both drug-free and azelaic acid-loaded nanoparticles, with concentration-dependent decreases in cell viability.

Conclusion: These results indicate a potential formulation for controlled release delivery of azelaic acid to the follicular unit.     

In vitro characterization studies of self-microemulsified bosentan systems

Context: Bosentan is a poorly soluble drug and pose challenges in designing of drug delivery systems.

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.