From global to local: impact assessment and social implications related to wind energy projects in Oaxaca,Mexico

In order to forecast likely impacts, Environmental Impact Assessment (EIA) has been applied worldwide. There are numerous social and cultural impacts that can hardly be addressed in a single EIA, and raise the awareness of social issues and proper assessment therein. This paper analyzes the social conflicts related to wind development projects in the Isthmus of Tehuantepec, Mexico using a qualitative approach. By conducting a Constellation Analysis (CA) in our case studies, this article aims at: 1) identifying the challenges and improvement opportunities for the social and environmental assessment of wind energy projects in Oaxaca, and 2) presenting CA as a novel approach to visualize and identify social and environmental issues. This paper emphasizes the relevance of earlier assessment of social implications to projects. This example can contribute to a better understanding of further research at Mexico’s regional and national levels, as well as in other regions or countries with similar development patterns.

Abbreviations: CA: Constellation Analysis; CDM: Clean Development Mechanism; CFE as in Spanish: Federal Electricity Commission; CIC: Community Interest Company; EIA: Environmental Impact Assessment; ESF: Environmental and Social Framework; FPIC: Free, Prior and Informed Consent; IFC: International Finance Corporation; ILO: International Labour Organization; LGEEPA as in Spanish: General Law on Ecological Balance and Environmental Protection; NEPA: National Environmental Policy Act; PDD: Project Design Document; SEMARNAT as in Spanish: Secretariat of Environment and Natural Resources; SENER as in Spanish: Secretariat of Energy; SIA: Social Impact Assessment; UNFCCC: United Nations Framework Convention on Climate Change; WB: World Bank.     

A comparison of drug substance predicted chemical stability with ICH compliant stability studies

Objective: The aim of this study is to demonstrate the applicability of predictive stability studies to the degradation of drug substances.

Significance: The use of predicted stability studies during pharmaceutical development and in regulatory submissions is increasing, particularly in early phase to support an initial retest period/shelf life claim in the absence of standard stability data. These studies offer an alternative to standard stability testing and can facilitate clinical trials to be started earlier and medicines to reach patients faster. They involve a short-term stressed stability study, typically designed to degrade a drug substance or product to the specification level of the shelf life limiting attribute. The results are used to predict degradation under long-term storage conditions and enable stability understanding to be gained over a short time frame, using limited amounts of material.

Methods: In this work, Accelerated Stability Assessment Program (ASAP) studies were performed for 10 different drug substances and the predictions obtained for chemical degradation were compared to ICH compliant stability data.

Results: Across the studies good agreement was achieved, with the initial retest period predictions from the ASAP studies being conservative by design. When minimal degradation was observed during an ASAP study, it was demonstrated that at least a 12-month initial retest period could be supported.

Conclusion: This comparison of ASAP predictions and ICH compliant stability data has demonstrated the ability of well-designed ASAP studies to predict the long-term chemical stability of drug substances.     

Determining what is important for sustainability: scoping processes of sustainability assessments

Over recent decades, there has been a significant proliferation of types of impact assessments. While some argue that this is threatening future use of impact assessments, sustainability assessments have emerged as a potential approach to bridge these diverse approaches. This research focuses on examining sustainability assessments at the project level, looking specifically at scoping practices key to integration. Nine multinational enterprises operating within Indonesia are studied, utilising a case study methodology with semi-structured interviews with 32 respondents. Findings emphasise that while these multinationals sought to address key regulatory requirements through their scoping practices, international standards and global sustainability platforms were critical in informing the practices of these organisations. The recognition of these standards and guidelines saw them addressing a broad range of key sustainability issues; also using prescribed techniques to engage with stakeholders and identify the most critical sustainability issues to focus on in assessment. There was integration of scoping processes through different levels and across the organisations, which were generally managed by teams providing sustainability expertise, including through affiliate personnel for local contextualisation.

Abbreviation AMDAL - Analisis Mengenai Dampak Lingkungan (EIA); BAPEDALDA - provincial/regional-level of the Environmental Impact Management Agency; CAQDAS – computer assisted data analysis software; CSR – corporate social responsibility; EIA – environmental impact assessment; EU – European Union; FDI – foreign direct investment; GRI – Global Reporting Initiative; ILO – International Labour Organization; MCA – multicriteria analysis; MNE – multinational enterprise; MOE - Ministry of Environment (now Ministry of Environment and Forestry); NGO – non-government organisation; OECD – Organisation for Economic Cooperation and Development; OH&S – occupational health and safety; SPPL - Letter of Statement on Environmental Management Effort; UKL – Environmental Management Effort; UN – United Nations; UNGC – United Nations Global Compact; UPL - Environmental Controlling Effort.     

Financial assessment of health and safety programmes in the workplace

In evaluating health and safety improvements for performance improvement, it is necessary to account for both the contributions of a healthy workforce and the resources required supporting it.

The Economic Assessment of the Work Environment (EAWE) is a financial framework that helps management forecast the financial benefits of health and safety implementations. The five-step process comprises (1) a health assessment to identify critical elements in the work environment, (2) an action plan to address gaps, (3) performance targets based on internal goals and external benchmarks, (4) transformation of the expected improvements in health and safety into expected performance outcomes, and (5) implementation in stages, starting from individual jobs to entire organisation.

EAWE offers a dynamic framework for corporate decision-makers when evaluating health and safety programmes. Further research should explore the bounds of EAWE across different types of organisations and the evolution of performance over time.     

Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid–phospholipid complex

Objective: To prepare and characterize an optimized phospholipid complex of Ursolic acid (UA) to overcome the poor pharmacokinetic properties and to investigate the impact of the complex on hepatoprotective activity and bioavailability in animal model.

Significance: UA is a potential phytoconstituent obtained from several plant sources, which has been explored for its diverse pharmacological activities including hepatoprotection. Its major limitation is poor absorption, rapid elimination, and hence low bioavailability after administration.

Methods: Response surface methodology was adopted to formulate an optimized (UA) complex. The complex was characterized by differential thermal analysis (DTA), Fourier transform-Infrared Spectroscopy, Powder X ray Diffraction, molecular docking, etc. The physico-chemical profile (solubility, oil/water partition coefficient) and in vitro dissolution profile was estimated. The formulation was then used to study hepatoprotective activity and bioavailability in animal models.

Results: Results showed that the phospholipid complex of UA has enhanced the hepatoprotective potential as compared to pure UA at the same dose level. The complex restored the levels of serum hepatic marker enzymes with respect to untreated group and increased the relative bioavailability of UA in rat plasma by 8.49-fold in comparison with pure compound at the same dose level. It enhanced the elimination half-life (t_{1/2 el}) from 0.69 ± 1.76 to 8.28 ± 1.98 h.

Conclusion: Complexation of UA with phospholipid markedly enhanced the hepatoprotective potential of UA by improving its bioavailability and pharmacokinetic parameters.

Novelty statement

The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.

Novelty statement

The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.     

Research on the relationship between cephalosporin structure,solution clarity,and rubber closure compatibility using volatile components profile of butyl rubber closures

Objective: Establish an effective experimental strategy to determine the compatibility of rubber closures for drugs.

Significance: Various types of rubber closures with different compositions are available for drug packaging. Many additives of rubber closures can be released from rubber closures and may affect the quality of drugs and pose a risk to human health. In this study, we aimed to determine the relationship between cephalosporin structure, solution clarity, and rubber closure compatibility using volatile components profile of butyl rubber closures.

Methods: Two opposite polarity gas chromatography (GC) systems and GC-mass spectrometry (MS) were used to achieve rapid qualitative determination of the main volatile components in rubber closures. Simulated adsorption experiment was performed to investigate the adsorption of main volatile components in rubber closures by cephalosporins with different side chain structures, and to determine the effects of adsorption on solution clarity.

Results: A volatile components screening library of rubber closures was established and the structures of some volatile component were confirmed. The specific adsorption of the structure of cephalosporins on volatile components from rubber closures was studied.

Conclusion: Based on the results of this study, rubber closures with good compatibility for cephalosporins with different side chain structures can be selected rapidly. This experimental strategy not only facilitates the screening of suitable rubber closures more effectively, but also enables the quick determination of volatile components adsorbed by drugs.     

The effect of ferrous ions,calcium ions and citric acid on absorption of ciprofloxacin across caco-2 cells: practical and structural approach

Objective: To study the potential influence of selected metal ions on absorption (and hence oral bioavailability of ciprofloxacin (Cipro) in presence and absence of a competing ligand.

Significance: The presence of metal ions together with Cipro results in complexes exhibiting a decreased bioavailability. Attempts were made to better understand the mechanism of decreased Cipro bioavailability in the presence of metals such as calcium and ferrous ions, and a small-sized ligand citric acid (CitA).

Methods: Effect of complex size or other potential factors was studied using diffusion through synthetic membrane, permeation studies across Caco-2 cells and capillary electrophoresis. A molecular dynamics (MD) simulation study was conducted to find the arrangement and the nature of the interactions between Cipro molecules and ferrous ions.

Results: Cipro was shown to form complexes with metals and CitA. The presence of CitA improved permeation of Cipro through the synthetic membrane but this was not as obvious in case of Caco-2 cells. Capillary electrophoresis suggested the existence of large molecular aggregates of Cipro: metal complexes. MD simulations offered clear evidence of large size aggregates in line with the experimental findings. CitA alone significantly improved permeation of Cipro through Caco-2 cells.

Conclusions: The size of the formed complexes, rather than the decrease in the solubility of formed complexes, plays a significant role in permeation (absorption) of Cipro. CitA might ameliorate the effect of co-administered metal ions on the bioavailability of Cipro.     

Proof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugs

Objectives: To carry out a proof-of-concept study on the development of dual-drug amorphous nanoparticle complex (nanoplex in short) as a potential formulation platform for fixed-dose combination (FDC) of poorly-soluble drugs.

Significance: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability.

Methods: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs.

Results: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160–410?nm and ?35–50?mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level.

Conclusion: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs.     

Physicochemical characterization and thermal behavior of hexosomes containing ketoconazole as potential topical antifungal delivery system

Objective: The main purpose of this article is to show the valuable characteristics that liotropic liquid crystal systems possess to be employed as new drug delivery systems.

Significance: Colloidal aqueous dispersions of lyotropic liquid crystal mesophases such as the identified as cubosomes and hexosomes, and so on, have received considerable attention due to their unique nanostructures and their thermodynamic properties, which provide the potential as a sustained drug release matrix. Additionally, their large surface area and similarity with the liquid crystal structures of intercellular lipids of stratum corneum enhances the interaction with the skin and mucous, increasing the potential for topical drug delivery efficiency of biopharmaceutical class II drugs as the antifungal ketoconazole.

Methods: This article presents the results in morphological characteristics, particle size, ζ potential, flow, thermal behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K) obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and water mixtures.

Results: This colloidal system exhibits a Newtonian-type flow and a hexagonal nanostructure with a median particle size of 107?±?20?nm and ζ potential of +4.45?±?0.50?mV. Through differential scanning calorimetry studies, the LHLC-K demonstrated physical and chemical stability for more than six months and mesophasic thermal reversibility between 10 and 50?°C. Finally, LHLC-K releases ketoconazole following a kinetics described by the first order model.

Conclusions: Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms.     

Dual cross-linked chitosan microspheres formulated with spray-drying technique for the sustained release of levofloxacin

Objective: This study was aimed to develop sustained drug release from levofloxacin (LF)-loaded chitosan (CS) microspheres for treating ophthalmic infections.

Significance: Dual cross-linked CS microspheres developed by the spray-drying technique displays significantly higher level of sustained drug release compared with non-cross-linked CS microspheres.

Methods: LF-loaded CS microspheres were prepared using the spray-drying technique, and then solidified with tripolyphosphate and glutaraldehyde as dual cross-linking agents. The microspheres were characterized by surface morphology, size distribution, zeta potential, encapsulation efficiency, and drug release profiles in vitro. The drug quantification was verified and analyzed by high-performance liquid chromatography (HPLC). The structural interactions of the CS with LF were studied with Fourier transform infrared spectroscopy. The effect of various influencing excipients in the formulation of the dual cross-linked CS microspheres on drug encapsulation efficiency and the drug release profiles were extensively investigated.

Result: The microspheres demonstrated high encapsulation efficiency (72.4?～?98.55%) and were uniformly spherical with wrinkled surface. The mean particle size was between 1020.7?±?101.9 and 2381.2?±?101.6?nm. All microspheres were positively charged (zeta potential ranged from 31.1?±?1.32 to 42.81?±?1.55?mV). The in vitro release profiles showed a sustained release of the drug and it was remarkably influenced by the cross-linking process.

Conclusion: This novel spray-drying technique we have developed is suitable for manufacturing LF-loaded CS microspheres, and thus could serve as a potential platform for sustained drug release for effective therapeutic application in ocular infections.     

Influencing factors on gelatin matrix for chlorhexidine delivery

Objective: The objective was to evaluate the influencing factors in the fabrication of gelatin matrix (gelatin chips) for drug delivery. The attributes affecting drug release characteristics of the gelatin products were examined.

Significance: Understanding the attributes that affect drug release from gelatin matrix could provide the knowledge base for the development, manufacturing, and performance evaluation of gelatin-based drug products for sustained drug delivery.

Methods: Chlorhexidine (CHX) was the model drug in the gelatin-product testing. The gelatin products were fabricated by two methods: a single-pot mixing of all the components and a two-step gelatin crosslinking followed by drug loading. Different gelatin types (Type A porcine and Type B bovine), glutaraldehyde (GTA) crosslinking conditions, glycerin concentration, and CHX concentration in drug loading and loading time were used to fabricate the products. The cumulative amounts of CHX release from the gelatin products were determined using in vitro release testing (IVRT).

Results: The attributes affecting CHX release from the gelatin products were gelatin type, GTA crosslinking, and CHX loading concentration. The fabrication methods (two-step method of gelatin crosslinking and drug loading by equilibration vs. direct mixing of the components) also affected CHX release. Other attributes such as glycerin and CHX loading time did not show significant effects on drug release under the conditions studied. In addition, the results in the two IVRT methods employed in this study were comparable.

Conclusion: Gelatin products of qualitative (Q1) and quantitative (Q2) differences could lead to different drug release behaviors. Drug release was also affected by the ingredient mixing steps during gelatin chip fabrication.     

SCC4 cell monolayers as an alternative sublingual barrier model: influence of nanoencapsulation on carvedilol transport

Objective: To evaluate, for the first time, the use of SCC4 cell monolayers as an alternative sublingual barrier model and study the influence of nanoencapsulation on carvedilol transport across SCC4 cell monolayers.

Significance: The sublingual cavity is an interesting route for administration of drugs with limited oral bioavailability due to hepatic first pass metabolism. By this route, the drug is directly absorbed into blood circulation. In this sense, mucoadhesive carvedilol-loaded nanocapsules (CAR-NC) were previously proposed for the administration of this drug by sublingual route. Carvedilol is used for cardiovascular diseases and suffers metabolism in liver when orally administrated. Nanoencapsulation of carvedilol controlled its permeation across porcine sublingual mucosa.

Methods: Carvedilol-loaded cationic nanocapsules were prepared by interfacial deposition of a preformed polymer. Drug permeation studies were carried out in Transwell^® inserts. The integrity of cell monolayers after the drug transport was assessed by transepithelial electric resistance. Compatibility of the CAR-NC with the SCC4 cells was evaluated by the Sulforhodamine B assay.

Results: The drug permeated the cell monolayer by a controlled way when nanoencapsulated and this profile had a linear relation with those observed in porcine sublingual mucosa. The integrity of the cell monolayer was maintained after drug permeation and CAR-NC was no cytotoxic to SCC4 cells.

Conclusion: Nanoencapsulated carvedilol permeated by a controlled and safe way by SCC4 cell monolayer. SCC4 cells monolayers may be used as in vitro model for sublingual drug transport studies in the development of novel formulations.     

Inhalable liposomes of Glycyrrhiza glabra extract for use in tuberculosis: formulation,in vitro characterization,in vivo lung deposition,and in vivo pharmacodynamic studies

Objective: The current study involves the development of liposomal dry powder for inhalation (LDPI) containing licorice extract (LE) for use in tuberculosis.

Significance: The current epidemiology of tuberculosis along with the increasing emergence of resistant forms of tuberculosis necessitates the need for developing alternative efficacious medicines for treatment. Licorice is a medicinal herb with reported activity against Mycobacterium tuberculosis.

Methods: Liposomes with LE were prepared by thin film hydration technique and freeze dried to obtain LDPI. The comprehensive in vitro and in vivo characterization of the LDPI formulation was carried out.

Results: The particle size of liposomes was around 210?nm with drug entrapment of almost 75%. Transmission electron microscopy revealed spherical shape of liposome vesicles. The flow properties of the LDPI were within acceptable limits. Anderson Cascade Impactor studies showed the mean median aerodynamic diameter, geometric standard deviation and fine particle fraction of the LDPI to be 4.29?µm, 1.23, and 54.68%, respectively. In vivo lung deposition studies of LDPI in mice showed that almost 46% of the drug administered reaches the lungs and 16% of administered drug is retained in the lungs after 24?hours of administration. The in vivo pharmacodynamic evaluation of the LDPI showed significant reduction in bacterial counts in lungs as well as spleen of TB-infected mice.

Conclusions: LE LDPI thus has a promising potential to be explored as an effective anti-tubercular medicine or as an adjunct to existing anti-tubercular drugs.     

Brain targeting of chitosan-based diazepam mucoadhesive microemulsions via nasal route: formulation optimization,characterization, pharmacokinetic and pharmacodynamic evaluation

Objective: The aim of present investigation was to develop microemulsions (MEs) and mucoadhesive microemulsions (MME) of diazepam for brain uptake through nasal administration for the treatment of seizure emergency.

Significance: Status epilepticus (SE) is a medical emergency, requires intravenous administration of diazepam which requires hospitalization of patient. Initiation of therapy at home via nasal administration of diazepam could prevent the damage of brain due to delay of therapy initiation.

Methods: Diazepam MEs were prepared by phase titration method, optimized by using Box–Behnken design. The influence of independent variables oleic acid, surfactant mixture (tween 80:propylene glycol), and water on dependent variables size, flux, and zeta potential was investigated. Optimized MEs, MMEs, and Calmpose (i.v route) were evaluated for pharmacokinetic and pharmacodynamic studies on rats.

Results: MME2 composed of oleic acid (5), surfactant mixture (50), water (45), and chitosan (0.5) showed size of 96.45?nm, PDI 0.21 and zeta potential 13.52?mV. MME2 showed significantly high flux of 846.96?±?34?µg/cm2/h and AUCbrain 1206.49?±?145.8. The drug targeting efficiency (314%) and direct nose-to-brain transport (68.1%) of MME2 were significantly high compared to Calmpose (i.v) and ME. The latency periods of minimal clonal seizures and generalized tonic–clonic seizures of MME2 was significantly increased (p?<?0.0001) compared to drug solution and Calmpose (i.v).

Conclusion: The brain uptake of diazepam from chitosan-based MMEs via nasal route is significantly high compared to i.v route.     

Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis,characterization, and pharmacokinetics

Objective: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability.

Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.

Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and ¹H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35?mg/kg for pharmacokinetic studies in Sprague Dawley rats.

Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73?mg/mL, which exhibited a sustained release pattern over 72?h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T_1/2 and AUC_0–∞, respectively, as compared to RH suspension.

Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.     

Dithranol-loaded nanostructured lipid carrier-based gel ameliorate psoriasis in imiquimod-induced mice psoriatic plaque model

Objective: The aim of this study was to formulate nanostructured lipid carriers (NLCs) of dithranol-loaded in gel for ease of application and to evaluate its anti-psoriatic efficacy vis-a-vis conventional ointment formulation.

Significance: This study will provide an insight about the use of nanocarriers, esp. NLCs loaded with dithranol for the effective treatment of psoriasis.

Methods: Dithranol-loaded NLCs were prepared by hot melt homogenization method and characterized for particle size and percentage entrapment efficiency. The optimized NLCs were loaded into gel and evaluated for drug release, spreadability, rheological behavior, and staining. Anti-psoriatic efficacy of the NLC gel was evaluated in imiquimod (IMQ) induced psoriatic plaque model in comparison with prepared conventional ointment formulation (1.15% w/w dithranol).

Results: NLCs were prepared with particle size below 300?nm, polydispersity index (PDI) below 0.3 and percentage entrapment efficiency of ～100%. The prepared NLC gel was then compared with the ointment for drug release, staining property, and efficacy. Topical application of dithranol-loaded NLC gel on IMQ-induced psoriatic plaque model reduced the symptoms of psoriasis assessed by both Psoriasis area severity index (PASI) scoring and enzyme-linked immunosorbent assay. There was a significant reduction in disease severity and cytokines like Interleukins-17, 22, 23 and Tumor necrosis factor-α by the developed system in comparison to the negative control.

Conclusions: To conclude dithranol-loaded NLCs in gel base was efficacious in management of psoriasis at the same drug concentration and also offer less cloth staining to that of the ointment product.     

A complex network approach to environmental impact assessment

This article proposes a complex network methodology for the process of Environmental Impact Assessment (EIA) that limits subjectivity and reduces uncertainty by incorporating elements of complex systems theory in the stages of identification and assessment of the significance of environmental impacts. The proposed methodology reduces the sources of uncertainty, which emerge from the use of simplified models that analyse the environment-activity interactions in a unidirectional fashion. This proposal determines the significance of environmental impacts through multidirectional or complex causal relationships. Likewise, it limits the subjectivity of the evaluator by using these causality relationships instead of criteria based on the impacts’ attributes. The application of the proposed methodology demonstrates the advantages of (i) prioritizing the impacts according to their capacity to interact with other impacts, and (ii) the possibility to redirect the environmental management plans towards the prevention of impacts of higher complexity and to reduce the importance of derived impacts.

The application of the proposed methodology reveals that the percentage of irrelevant and moderate impacts is reduced, whereas the percentage of severe and critical impacts increase, in comparison to the conventional methodologies.     

Effect of semicrystalline copolymers in solid dispersions of pioglitazone hydrochloride: in vitro-in vivo correlation

Objective: The study was aimed to improve the dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water-soluble drug.

Significance: Poor aqueous solubility of PGH was overcome by the design of SDs. Level A correlation demonstrated between in vitro release and bioavailability of PGH, suggest its biowaiver potential.

Methods: The effects of semicrystalline copolymers (poloxamer 407 and gelucire 50/13) and methods of preparations on dissolution behavior, in vivo performance, and stability of PGH SDs were investigated. All the SDs were characterized by FTIR, TGA, DSC, XRD, and SEM.

Results: FTIR and TGA showed the compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns & SEM indicated a change from a crystalline to an amorphous state. Gelucire 50/13 was observed to have greater ability to form SDs than poloxamer 407 in solvent evaporation method (SM). Prevention of recrystallization during storage suggested stability of the formulation. Gelucire 50/13 based SD, prepared by SM remarkably increased the dissolution within 15?min (87.27?±?2.25%) and was supported by dissolution parameters (Q₁₅, IDR, RDR, % DE, f₁, f₂). These SDs showed pH-dependent solubility. In vivo test showed significantly (p?<?.05) higher AUC_0–t and C_max, which were about 3.17 and 4.34 times that of the pure drug respectively.

Conclusion: Gelucire 50/13 was found to be a suitable carrier for SM for preparation of SDs of PGH as evident from increased dissolution and bioavailability.