Formulation Strategies Research Articles

Driving enterprise transformation

This study investigates how organisational and geographical factors affect the efficacy of business architecture in enterprises. Employing a quantitative research methodology, the research analyses data from a diverse range of organisations using ordinal logistic regression. The findings validate the hypothesis that factors like organisational alignment, industry sector, geographic region, organisational size, and adoption duration significantly influence business architecture's maturity and strategic impact. The study contributes to the understanding of business architecture's role in organisational strategy, highlighting the importance of contextual factors. It suggests that business architecture strategies should be tailored to specific organisational contexts, offering valuable insights for policy formulation and organisational strategy development. This research provides a foundation for future studies and practical applications in business architecture and enterprise transformation, emphasizing the need for a nuanced approach considering different organisational and regional characteristics.

Liposomal Formulation Reduces Transport and Cell Uptake of Colistin in Human Lung Epithelial Calu-3 Cell and 3D Human Lung Primary Tissue Models.

Respiratory tract infections caused by multi-drug-resistant (MDR) bacteria have been a severe risk to human health. Colistin is often used to treat the MDR Gram-negative bacterial infections as a last-line therapy. Inhaled colistin can achieve a high concentration in the lung but none of aerosolized colistin products has been approved in the USA. Liposome has been reported as an advantageous formulation strategy for antibiotics due to its controlled release profile and biocompatibility. We have developed colistin liposomal formulations in our previous study. In the present study, the cellular uptake and transport of colistin in colistin liposomes were examined in two human lung epithelium in vitro models, Calu-3 monolayer and EpiAirway 3D tissue models. In both models, cellular uptake (p < 0.05) and cellular transport (p < 0.01) of colistin were significantly reduced by the colistin liposome compared to the colistin solution. Our findings indicate that inhaled colistin liposomes could be a promising treatment for extracellular bacterial lung infections caused by MDR Pseudomonas aeruginosa (P. aeruginosa).

Supramolecular dye nanoassemblies for advanced diagnostics and therapies.

Dyes have conventionally been used in medicine for staining cells, tissues, and organelles. Since these compounds are also known as photosensitizers (PSs) which exhibit photoresponsivity upon photon illumination, there is a high desire towards formulating these molecules into nanoparticles (NPs) to achieve improved delivery efficiency and enhanced stability for novel imaging and therapeutic applications. Furthermore, it has been shown that some of the photophysical properties of these molecules can be altered upon NP formation thereby playing a major role in the outcome of their application. In this review, we primarily focus on introducing dye categories, their formulation strategies and how these strategies affect their photophysical properties in the context of photothermal and non-photothermal applications. More specifically, the most recent progress showing the potential of dye supramolecular assemblies in modalities such as photoacoustic and fluorescence imaging, photothermal and photodynamic therapies as well as their employment in photoablation as a novel modality will be outlined. Aside from their photophysical activity, we delve shortly into the emerging application of dyes as drug stabilizing agents where these molecules are used together with aggregator molecules to form stable nanoparticles.

Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP

ObjectivesThe therapeutic delivery of hydrophobic drugs via solid dispersion is an appealing methodology to enhance the dissolution rate and ultimately the in vivo bioavailability. The objective of current investigation was to enhance the solubility of anti-tubercular drug bedaquiline fumarate (BQF) via solid dispersion strategy, where the influence of polyethylene glycol and polyvinylpyrrolidone on the performance of solid dispersions was determined. MethodsBQF-solid dispersions with polyethylene glycol and polyvinylpyrrolidone were fabricated via solvent evaporation technique and evaluated for solubility, in vitro dissolution studies, cytotoxicity, cellular uptake, intestinal permeability, and pharmacokinetics. ResultsSolubility of BQF was improved by 6.4-fold and 13.44-fold with polyethylene glycol and polyvinylpyrrolidone-based ternary solid dispersions, respectively. The in vitro dissolution studies revealed significant enhancement in dissolution rate of BQF. The in vivo pharmacokinetic results demonstrated that solid dispersions significantly improved the pharmacokinetic parameters of BQF. The relative bioavailability of BQF with polyvinylpyrrolidone-based ternary solid dispersion was found to be enhanced by 173% and 154%, under fasted and fed state, respectively, when compared to BQF suspension. ConclusionsOur study reaffirms the applicability of solid dispersions as an alternative formulation strategy to improve the biopharmaceutical attributes of BQF in tuberculosis therapy.

Localized Rectal Cancer: Indian Consensus and Guidelines

AbstractThe rising incidence of colorectal cancer (CRC) in India, particularly the prevalence of rectal cancer over colon cancer (0.7:1), has been a growing concern in recent decades; especially notable is the trend of increasing cases among young CRC patients. Given the diverse treatment approaches for rectal cancer globally and the varying economic capacities of patients in low to middle-income countries (LMICs) like India, it is essential to establish consensus guidelines that are specifically tailored to meet the needs of these patients. To achieve this, a panel comprising 30 eminent rectal cancer experts convened to conduct a comprehensive and impartial evaluation of existing practices and recent advancements in the field. Through meticulous scrutiny of published literature and a consensus-building process that involved voting on pertinent questions, the panel formulated management strategies. These recommendations are the result of a rigorous, evidence-based process and encapsulate the collective wisdom and judgment of leading authorities in the field.

Computational Screening for mAb Colloidal Stability with Coarse-Grained, Molecular-Scale Simulations.

Monoclonal antibodies (mAbs) are an important modality of protein therapeutics with broad applications for numerous diseases. However, colloidal instabilities occurring at high protein concentrations can limit the ability to develop stable, high-concentration liquid dosage forms that are required for patient-centric, device-mediated products. Therefore, it is advantageous to identify colloidally stable mAbs early in the discovery process to ensure that they are selected for development. Experimental screening for colloidal stability can be time- and resource-consuming and is most feasible at the later stages of drug development due to material requirements. Alternatively, computational approaches have emerging potential to provide efficient screening and focus developmental efforts on mAbs with the greatest developability potential, while providing mechanistic relationships for colloidal instability. In this work, coarse-grained, molecular-scale models were fine-tuned to screen for colloidal stability at amino-acid resolution. This model parameterization provides a framework to screen for mAb self-interactions and extrapolate to bulk solution behavior. This approach was applied to a wide array of mAbs under multiple buffer conditions, demonstrating the utility of the presented computational approach to augment early candidate screening and later formulation strategies for protein therapeutics.

Biopolymer Packaging Materials in the Pharmaceutical Industry

Biopolymer packaging materials are gaining prominence in the pharmaceutical industry due to environmental concerns. Derived from renewable sources, these biopolymers offer biodegradability, biocompatibility, and non-toxicity, making them ideal for various pharmaceutical applications. In drug delivery, biopolymers play a crucial role in controlled release formulations, especially for personalized medicines and biopharmaceutical products. Hydrogels, three-dimensional polymer networks, are key in mimicking living tissues and facilitating stimuli-responsive drug release with minimal toxic effects. The formulation strategies involve diffusion-controlled, degradation-controlled, or environmentally triggered release. Biodegradable systems, using polymers like poly(lactic acid) and poly(glycolic acid), contribute to sustainable drug delivery by undergoing controlled degradation. Osmotic delivery systems leverage osmotic pressure for controlled drug release, while stimuli-responsive designs respond to environmental changes. Biopolymer integration in pharmaceutical packaging aligns with eco-friendly practices, addressing challenges posed by traditional petroleum-based materials. This shift signifies a sustainable and innovative approach to pharmaceutical packaging in harmony with environmental preservation.

L-arginine–phosphatidylcholine thermoresponsive gel for enhanced transdermal delivery and L-929 cell cytotoxicity evaluation

The vasodilator effect of the semi-essential amino acid, L-arginine (LA) is crucial in the clinical management of angina pain and erectile dysfunction. Moreover, the limited bioavailability and the drug’s polar nature navigate the development of new formulation strategies for effective transdermal delivery, especially for the penile route. Thus, herein, we prepared the L-arginine–phosphatidylcholine (LA–PC) complex by solvent evaporation technique and converted it into a thermoresponsive gel (LA–PC gel). The optimized complex was selected for the preparation of gel using poloxamer 407, lactic acid, and purified water. Simultaneously we prepared the LA thermoresponsive gel (LA gel). The gels were characterized for their appearance, particle size, pH, osmolality, spreadability, SEM, FTIR, viscosity, TEM, viscoelastic properties, and skin permeability using the Strat-M® membrane at low pH for effective and safe penile and vaginal delivery. We observed that the LA–PC gel showed the smallest droplet size (<100 nm), a zeta potential of −59 mV indicates its stability with good viscoelastic behavior. The in vitro skin permeation reveals that; at 15 min, the permeation of LA for LA–PC gel, was 33.20% with a flux of 2.19 mg/cm2/min, and in the case of LA gel, the permeation of LA was only 18% at 45 minutes with a flux of 1.02 mg/cm2/min. The in vitro cytocompatibility was conducted using an L-929 cell line, and we found that both gels were nontoxic up to 100 µg/mL concentration. In summary, LA–PC gel could have a significant impact on the quick and sustained release, compared to LA gel.

Organogels: "GelVolution" in Topical Drug Delivery - Present and Beyond.

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.

An overview of essential oil-based nanoemulsion and their biological activities against some microbial pathogenic

The essential oils are constantly increasing due to their biological activities utilization in several fields, from agricultures to pharmaceuticals. However, their extensively use are still limited due to their disreputable physico-chemical properties. Nowadays, the most appropriate to overcome such restrictions is to develop of the proper formulation strategies. One of the oncoming prompted to achieve this goal is through nanoemulsions. Nanoemulsion are heterogeneous dispersions or a colloidal particulate system in the submicron size range acting as carriers of drug molecules. Nanoemulsion is most studied in encapsulation process due to inexpensive in their manufacturing, ease of formulation and easy waste handling. In this review, intends to offer an overview of the formulation, preparation of essential oil-based nanoemulsion and their biological activities against some microbial pathogenic.

Curcumin Delivery Systems: How Far from Clinical Application in Tumor Therapy?

Curcumin, a natural polyphenol compound found in turmeric, exhibits significant anti-cancer activity in preclinical studies. However, its clinical application is limited by poor bioavailability and low solubility in aqueous media. To overcome these challenges, various curcumin delivery systems (CDSs) have been developed to enhance the pharmacokinetics and pharmacodynamics of curcumin, aiming to improve its solubility, stability, and targeted delivery to tumor cells. Preclinical studies have shown that CDSs can improve pharmacokinetics, enhance anti-tumor efficacy, and reduce toxicity in various cancers. Several CDSs have also advanced into clinical trials, demonstrating safety and efficacy in cancer patients. Despite the promising results, challenges remain, such as optimizing formulation and dosage, investigating curcumin's influence on the carriers in drug delivery and release, evaluating long-term safety and toxicity, and conducting large-scale clinical trials. Understanding the effect of gut microbiota on CDSs metabolism and bioavailability is critical for enhancing their clinical effectiveness in tumor therapy. Further research and development are necessary to fully exploit the potential of CDSs in cancer treatment. This review summarizes recent progress in CDSs research and their potential application in tumor therapy, encompassing formulation strategies, delivery routes, as well as preclinical and clinical evaluations. It not only provides valuable insights into the future rational design and development of curcumin dosage forms and their cancer therapeutic potential but also facilitates the clinical translation of curcumin and CDSs.

Formulation of Telkomproperty's Strategy in Realizing an Outstanding Property Company

In facing competition and environmental changes, TelkomProperty needs to formulate a strategy by identifying internal resources and external conditions in an effort to achieve a competitive advantage. These factors can facilitate the formulation of strategies that can develop TelkomProperty's business. The formulated strategies should also be aligned with the components of Corporate Real Estate Management (CREM). To achieve these goals, the methods used include observation, literature study of relevant theories, and interviews with related informants. The data obtained are analyzed and strategies are formulated with external analysis using PEST analysis (Political, Economic, Social, and Technological). Then, internal analysis is conducted using the Resource-Based View approach and VRIO analysis. The results of the research indicate that TelkomProperty has 3 opportunities and 5 threats with an EFE matrix score of 2.54. TelkomProperty has 13 strengths and 9 weaknesses with an IFE matrix score of 2.84. From the VRIO analysis, TelkomProperty's internal strengths include 4 strengths that fall into the category of sustained competitive advantage. Based on the IE matrix and SWOT analysis, 6 alternative strategies were identified. The best alternative strategy was then determined using QSPM. The chosen strategy is to integrate the Internet of Things into the MyBirawa and MyDEFA applications to enhance the modern experience for customers, making it a distinctive feature of TelkomProperty with the highest STAS value of 3.32.

Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

Novel Advancements in Mouth Dissolving Film Technology

Mouth dissolving film (MDF) technology has emerged as an innovative drug delivery platform offering rapid drug absorption and enhanced patient compliance. This comprehensive review explores recent advancements in MDF technology, focusing on formulation strategies, manufacturing techniques, and applications in pharmaceutical and nutraceuticals industries.

Controlling stabilization of oil‐in‐water emulsions with lignins through fractionation, functionalization, and formulation

AbstractLignins, heterogeneous assemblies of polyphenolic oligomers present in lignocellulosic plant biomass, are valorized mainly by combustion because of their low solubility in commonly used solvents. However, in addition to antioxidant, anti‐UV and antimicrobial properties, and marked interfacial properties are part of lignins physicochemical properties, thus making them good candidates for sustainable colloids. It is hypothesized that lignins solubility and emulsifying performances could be modulated by fractionation, functionalization, and formulation strategies. The importance of the solvent, and of the pH on lignins solubilization in aqueous phase was investigated. Accordingly, simple O/W emulsions stabilized by different lignins were designed and characterized. The whole results demonstrated that lignins solubility in water can be optimized using appropriate co‐solvent and pH readjustment resulting in a homogeneous dispersion with only 7.2 ± 1.8% wt/wt of insoluble lignins. Both fractionation and biocatalytic modification of lignins allowed increasing stabilization of the oil–water interface by limiting coalescence (23%–24% of relative increase of the D90) compared with non‐fractionated lignins (32%), thus advocating their potential use as multifunctional emulsion stabilizers. As a result, a direct link between the molar mass profile of lignins and their ability to stabilize the oil–water interface as well as to reduce emulsion's sedimentation could be established.

Advancing Drug Delivery Paradigms: Polyvinyl Pyrolidone (PVP)-Based Amorphous Solid Dispersion for Enhanced Physicochemical Properties and Therapeutic Efficacy.

The current challenge in drug development lies in addressing the physicochemical issues that lead to low drug effectiveness. Solubility, a crucial physicochemical parameter, greatly influences various biopharmaceutical aspects of a drug, including dissolution rate, absorption, and bioavailability. Amorphous solid dispersion (ASD) has emerged as a widely explored approach to enhance drug solubility. The objective of this review is to discuss and summarize the development of polyvinylpyrrolidone (PVP)-based amorphous solid dispersion in improving the physicochemical properties of drugs, with a focus on the use of PVP as a novel approach. This review was conducted by examining relevant journals obtained from databases such as Scopus, PubMed, and Google Scholar, since 2018. The inclusion and exclusion criteria were applied to select suitable articles. This study demonstrated the versatility and efficacy of PVP in enhancing the solubility and bioavailability of poorly soluble drugs. Diverse preparation methods, including solvent evaporation, melt quenching, electrospinning, coprecipitation, and ball milling are discussed for the production of ASDs with tailored characteristics. PVP-based ASDs could offer significant advantages in the formulation strategies, stability, and performance of poorly soluble drugs to enhance their overall bioavailability. The diverse methodologies and findings presented in this review will pave the way for further advancements in the development of effective and tailored amorphous solid dispersions.

Incorporating surfactants into PCL microneedles for sustained release of a hydrophilic model drug

Polymeric microneedles (MNs) are widely used for sustained drug release due to their distinct advantages over other types of MNs. Poly-ε-caprolactone (PCL) stands out as a biodegradable and biocompatible hydrophobic polymer commonly employed in drug delivery applications. This study explores the impact of surfactants on the encapsulation and release rate of a model hydrophilic drug, minoxidil (MXD), from PCL MNs. Three nonionic surfactants, Tween 80, Span 60, and polyethylene glycol (PEG), were integrated into PCL MNs at varying concentrations. Compared to the other types of surfactants, PEG-containing PCL MNs exhibit enhanced insertion capabilities into a skin-simulant parafilm model and increased mechanical strength, suggesting facile penetration into the stratum corneum. Furthermore, MXD-PEG MNs show the highest encapsulation efficiency and are further characterized using FTIR, DSC and XRD. Their mechanical strength against different static forces was measured. The MNs exhibit a sustained release pattern over 20 days. Eventually, MXD-PEG MNs were subjected to penetration testing using chicken skin and required minimal insertion forces with no observed MN failure during experimentation even after compression with the maximum force applied (32 N per patch). Taken together, the present work demonstrates the feasibility of incorporating nonionic surfactants like PEG into the tips of hydrophobic PCL MNs for sustained delivery of a model hydrophilic drug. This formulation strategy can be used to improve patient compliance by allowing self-administration and achieving prolonged drug release.

Chemistry and Art of Developing Lipid Nanoparticles for Biologics Delivery: Focus on Development and Scale-Up.

Lipid nanoparticles (LNPs) have gained prominence as primary carriers for delivering a diverse array of therapeutic agents. Biological products have achieved a solid presence in clinical settings, and the anticipation of creating novel variants is increasing. These products predominantly encompass therapeutic proteins, nucleic acids and messenger RNA. The advancement of efficient LNP-based delivery systems for biologics that can overcome their limitations remains a highly favorable formulation strategy. Moreover, given their small size, biocompatibility, and biodegradation, LNPs can proficiently transport therapeutic moiety into the cells without significant toxicity and adverse reactions. This is especially crucial for the existing and upcoming biopharmaceuticals since large molecules as a group present several challenges that can be overcome by LNPs. This review describes the LNP technology for the delivery of biologics and summarizes the developments in the chemistry, manufacturing, and characterization of lipids used in the development of LNPs for biologics. Finally, we present a perspective on the potential opportunities and the current challenges pertaining to LNP technology.

Formulation of lactoferrin decorated dextran based chitosan-coated europium metal-organic framework for targeted delivery of curcumin

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic ‘CS’ on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of ‘CUR’ in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the ‘CS’ coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when ‘Lf’ is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting ‘CUR’ to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.

Relationships between Dietary Chemical Components and Enteric Methane Production and Application to Diet Formulation in Beef Cattle

We used published data consisting of 263 treatment mean observations from beef cattle and dairy steers and heifers, in which CH4 was measured via chambers or head boxes, to evaluate relationships between enteric CH4 production and dry matter intake (DMI) and dietary components. Daily DMI was positively related (slope = 15.371, p &lt; 0.001) to total daily production (g/d) of CH4 (r2 = 0.821). Among chemical components, dietary neutral detergent fiber (NDF) concentration was the most highly related (r2 = 0.696; slope = 0.2001; p &lt; 0.001) to CH4 yield (g/kg of DMI), with strong relationships also noted for dietary starch:NDF ratio (r2 = 0.662; slope = −2.4587; p &lt; 0.001), starch (r2 = 0.495; slope = −0.106; p &lt; 0.001), and the proportion of metabolizable energy relative to gross energy (r2 = 0.561; slope = −23.663; p &lt; 0.001). The slope (−0.5871) and intercept (22.2295) for the dietary ether extract vs. CH4 yield were significant (p &lt; 0.001), but the relationship was highly variable (r2 = 0.150). For dietary crude protein concentration, the slope for CH4 yield was not significant (−0.0344; p &lt; 0.381) with an r2 value near zero. Decreasing DMI by programming body weight gain or restricting feed intake could decrease CH4 production in confined cattle, but these approaches might negatively affect growth performance and product quality, potentially negating positive effects on CH4 production. Feeding higher-quality forages or using grazing management systems that decrease dietary NDF concentrations or substituting grain (starch) for forage should decrease both CH4 yield from enteric production and manure CH4 production via increased digestibility. Effects of feeding management and diet formulation strategies should be additive with other mitigation approaches such as feed additives, allowing the cattle industry to achieve maximal decreases in enteric CH4 production, while concurrently maintaining optimal beef production.