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To investigate the effects of (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), tocopherol polyethylene glycol 1000 succinate (TPGS), sodium desoxycholate (SDOCH), trimethyl chitosan (TMC), and sodium caprate (C10) on the plasma concentration and the oral bioavailability of tigecycline in broiler chickens. To test the effects of the excipients on absorption of tigecycline, a tetracycline that is poorly absorbed from the gastrointestinal tract, broiler chickens were used as an animal model. Tigecycline (10 mg/kg body weight) was administered intravenously, orally, and orally with one of the excipients. Plasma samples were taken after administration. To measure tigecycline concentrations, high-performance liquid chromatography coupled with tandem mass spectrometry was used. Compartmental and non-compartmental analyses were used for pharmacokinetic analyses of mean plasma concentrations versus time. With the exception of sodium caprate, all the excipients significantly increased the area under the curve and bioavailability of tigecycline (p < 0.05). These parameters were approximately doubled by HP-β-CD, TPGS, and SDOCH, with 95% confidence intervals (95% CIs) for the difference that included only increases of 1.5-fold or higher (bioavailability: control, 1.67%; HP-β-CD, 3.24%; TPGS, 3.30%; and SDOCH, 3.24%). The increases in these parameters were smaller with DM-β-CD and TMC (DM-β-CD, 2.41%; TMC, 2.55%), and the 95% CIs ranged from close to no difference to nearly double the values in the control group. These results indicate that HP-β-CD, TPGS, and SDOCH substantially increase the area under the curve and oral bioavailability of tigecycline. They suggest that DM-β-CD and TMC may also substantially increase these parameters, but more research is needed for more precise estimates of their effects. [ABSTRACT FROM AUTHOR]

The way a drug molecule is administered has always had a profound impact on people requiring medical interventions - from vaccine development to cancer therapeutics. In the Controlled Release Society Fall Symposium 2022, a trans-institutional group of scientists from industry, academia, and non-governmental organizations discussed what a breakthrough in the field of drug delivery constitutes. On the basis of these discussions, we classified drug delivery breakthrough technologies into three categories. In category 1, drug delivery systems enable treatment for new molecular entities per se, for instance by overcoming biological barriers. In category 2, drug delivery systems optimize efficacy and/or safety of an existing drug, for instance by directing distribution to their target tissue, by replacing toxic excipients, or by changing the dosing reqimen. In category 3, drug delivery systems improve global access by fostering use in low-resource settings, for instance by facilitating drug administration outside of a controlled health care institutional setting. We recognize that certain breakthroughs can be classified in more than one category. It was concluded that in order to create a true breakthrough technology, multidisciplinary collaboration is mandated to move from pure technical inventions to true innovations addressing key current and emerging unmet health care needs. [ABSTRACT FROM AUTHOR]

A straightforward RP-HPLC approach has been developed and validated for the simultaneous estimation of Drotaverine hydrochloride (DROTA) and Diclofenac potassium (DICLO) in their combined dosage form. This method was found to be simple, accurate, and precise. Chromatographic detection has been carried out on a PhenomenexC18 column (250 mm×4.6 mm, i.d, 5 µm) with a flow rate of 1.0 mL/min using an isocratic mobile phase consisting of Methanol and Water (80:20v/v, pH3 adjusted with ortho phosphoric acid). The wavelength 280nm was chosen for the UV detection. The separation of DROTA and DICLO took less than ten minutes, had a good resolution, and produced very little tailing. There was no interference from any excipients. The method was validated in accordance with the ICH recommendations, and the criteria for accuracy, precision, linearity, and system adaptability were all satisfactory in each and every one of the cases. [ABSTRACT FROM AUTHOR]

Poly‐L‐lysine (PLL) is known to be an encapsulating agent in drug formulation and delivery. PLL also has apoptotic and antiproliferative activities that enable blocking of the tumorigenesis process. However, the dose‐selective activities of PLL in exerting apoptosis against cancer are unclear. Therefore, this study has been designed to explore the potential role and dose of PLL in apoptosis, if any. For this, PLL was administered at several doses in cancer cell lines and was found to be more potent against MCF‐7 cells. PLL causes mitochondria‐mediated apoptotic death through the upregulation of cleaved caspase‐3. To investigate the mechanism responsible for this activity, we have analyzed if PLL could have the DNA interactive property or not. For this, molecular docking analysis was carried out to prove whether it has the property to bind with DNA or not. Studies have revealed that PLL is a potent DNA binder and it probably performs such apoptotic activities through the binding of cellular DNA early in an exposure. Simultaneous upregulation of both ROS‐mediated stress and also in key protein expressions like γ‐H2AX could also help us to confirm that PLL induces apoptosis through DNA interaction. This finding leads us to believe that PLL could play an interfering role with other chemotherapeutic compounds when used as a drug‐coating material as it exerts an apoptotic effect on cancer cells, which should be avoided by using a much lower concentration. [ABSTRACT FROM AUTHOR]

The effect of Eudragit RSPO on the photostability of venlafaxine in a physical mixture and as a melt was studied. A validated ultra-high-performance liquid chromatography mass spectrometry method was used to determine the content of venlafaxine alongside degradation products. The most likely structures of the degradation products were determined by mass spectrometry. The samples were evaluated before and after exposure to ultraviolet A by differential scanning calorimetry and scanning electron microscopy. The kinetic parameters of the decomposition of venlafaxine in the physical mixture and melt form were calculated and comparable to those of venlafaxine as an active pharmaceutical ingredient. The results indicate that the process of venlafaxine decomposition is more than three times slower in the venlafaxine–eudragit melt than in its physical mixture with eudragit and its pure form. The strong photoprotective nature of the tested polymer against venlafaxine in the melt form was also confirmed by differential scanning calorimetry and scanning electron microscopy. [ABSTRACT FROM AUTHOR]

Palygorskite is an aluminum and magnesium silicate characterized by its fibrous morphology, providing it with great versatility in industrial applications, including pharmaceuticals. Although most of the reserves are in the United States, in recent years occurrences of commercially exploited deposits in Brazil have been recorded, mainly in the country's northeast region. This has motivated this study, which analyzes raw Brazilian palygorskite compared to a commercial sample (Pharmasorb® colloidal) to demonstrate its pharmaceutical potential. The chemical and mineral composition of the samples were evaluated for surface properties, granulometry, morphology, crystallography, thermal analysis, and spectroscopy. Raw palygorskite presented 67% purity, against 74% for Pharmasorb® colloidal. The percentage purity relates to the presence of contaminants, mainly carbonates and quartz (harmless under conventional conditions of pharmaceutical use). Furthermore, it was possible to confirm the chemical composition of these phyllosilicates, formed primarily of silicon, aluminum, and magnesium oxides. The crystallographic and spectroscopic profiles were consistent in both samples, showing characteristic peaks for palygorskite (2θ = 8.3°) and bands attributed to fibrous phyllosilicates below 1200 cm−1, respectively. The thermal analysis allowed the identification of the main events of palygorskite, with slight differences between the evaluated samples: loss of water adsorbed onto the surface (~85 °C), removal of water contained in the channels (~200 °C), coordinated water loss (~475 °C), and, finally, the dehydroxylation (>620 °C). The physicochemical characteristics of raw palygorskite align with pharmacopeial specifications, exhibiting a high specific surface area (122 m2/g), moderately negative charge (−13.1 mV), and compliance with the required limits for heavy metals and arsenic. These favorable technical attributes indicate promising prospects for its use as a pharmaceutical ingredient in the production of medicines and cosmetics. [ABSTRACT FROM AUTHOR]

Electrospun microfibers are emerging as one of the advanced wound dressing materials for acute and/or chronic wounds, especially with their ability to carry drugs and excipients at a high loading while being able to deliver them in a controlled manner. Various attempts were made to include excipients in electrospun microfibers as wound dressing materials, and one of them is poloxamer, an amphiphilic polymer that exhibits wound debridement characteristics. In this study, we formulated two types of poloxamers (i.e., P188 and P338) at 30% (w/w) loading into electrospun polycaprolactone (PCL) fibers to evaluate their physicomechanical properties, biocompatibility, and in vitro drug release of a model drug. Our findings showed that the incorporation of poloxamers in the PCL solutions during electrospinning resulted in a greater "whipping" process for a larger fiber deposition area. These fibers were mechanically stiffer and stronger, but less ductile as compared to the PCL control fibers. The incorporation of poloxamers into electrospun PCL fibers reduced the surface hydrophobicity of fibers according to our water contact angle studies and in vitro degradation studies. The fibers' mechanical properties returned to those of the PCL control groups after "dumping" the poloxamers. Moreover, poloxamer-loaded PCL fibers accelerated the in vitro release of the model drug due to surface wettability. These poloxamer-loaded PCL fibers were biocompatible, as validated by MTT assays using A549 cells. Overall, we demonstrated the ability to achieve a high loading of poloxamers in electrospun fibers for wound dressing applications. This work provided the basic scientific understanding of materials science and bioengineering with an emphasis on the engineering applications of advanced wound dressings. [ABSTRACT FROM AUTHOR]

Dexamethasone (DXM) is a potent glucocorticoid with an anti-inflammatory and anti-angiogenic activity which is widely clinically used. Systemic side effects limit the long-term use of DXM in patients requiring formulations which deliver and selectively release the drug to the diseased tissues. This in vitro study compares the suitability of DXM and commonly used prodrugs dexamethasone-21-phosphate (DXMP) and dexamethasone-21-palmitate (DP) as well as DXM complexed by 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) for the use in thermosensitive liposomes (TSL). DXM showed a poor retention and a low final drug:lipid ratio in a 1,2-dipalmitoyl- sn ‑glycero-3-phosphodiglycerol-based TSL (DPPG 2 -TSL) and a low-temperature sensitive liposome (LTSL). In contrast to DXM, DXMP and DP were stably retained at 37 °C in TSL in serum and could be encapsulated with high drug:lipid ratios in DPPG 2 -TSL and LTSL. DXMP showed a rapid release at mild hyperthermia (HT) from both TSL in serum, whereas DP remained incorporated in the TSL bilayer. According to release experiments with carboxyfluorescein (CF), HP-γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) are suitable vehicles for the loading of DXM into DPPG 2 -TSL and LTSL. Complexation of DXM with HP-γ-CD increased the aqueous solubility of the drug leading to approx. ten times higher DXM:lipid ratio in DPPG 2 -TSL and LTSL in comparison to un-complexed DXM. Both DXM and HP-γ-CD showed increased release at HT in comparison to 37 °C in serum. In conclusion, DXMP and DXM complexed by HP-γ-CD represent promising candidates for TSL delivery. [ABSTRACT FROM AUTHOR]

Aim: This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems. Methods: Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via 1H NMR, FTIR, as well as Ellman's test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus. Results: Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (m/v) and low cytotoxicity up to 2% (m/v). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA. Conclusion: Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity. [ABSTRACT FROM AUTHOR]

Specific aspects of semi-solid dosage forms for topical application include the nature of the barrier to be overcome, aspects of susceptibility to physical and chemical instability, and a greater influence of sensory perception. Advances in understanding the driving forces of skin penetration as well as the design principles and inner structure of formulations, provide a good basis for the more rational design of such dosage forms, which still often follow more traditional design approaches. This review analyses the opportunities and constraints of rational formulation design approaches in the industrial development of new topical drugs. As the selection of drug candidates with favorable physicochemical properties increases the speed and probability of success, models for drug selection based on theoretical and experimental approaches are discussed. This paper reviews how progress in the scientific understanding of mechanisms and vehicle-influence of skin penetration can be used for rational formulation design. The characterization of semi-solid formulations is discussed with a special focus on modern rheological approaches and analytical methods for investigating and optimizing the chemical stability of active ingredients in consideration of applicable guidelines. In conclusion, the combination of a good understanding of scientific principles combined with early consideration of regulatory requirements for product quality are enablers for the successful development of innovative and robust semi-solid formulations for topical application. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of magnesium myristate as a multifunctional excipient in the formulation of cosmetic liquid foundation and aimed to compare it with liquid foundations that use the conventional excipients. The formulation was evaluated for different parameters such as organoleptic, pH, viscosity, spreadability, adhesivity, hedonic test, storage stability at room temperature, and determination of sun protection factor (SPF) value using ultraviolet (UV)-visible spectrophotometry. The results confirmed that the liquid foundation formulated using magnesium myristate showed better results and stability because there was no change in its physical appearance, pH, and spreadability in comparison to the liquid foundation formulated using conventional excipients. The liquid foundation formulated using magnesium myristate recorded a moderate SPF value (11.02), which can be practical for daily use, especially in individuals with tanned skin. Therefore, we concluded that magnesium myristate contributed as an emulsifier, opacifier, viscosity controller, and smoothening agent with good spreadability, coverage, texture, and better UV protection in comparison to the mixture of different conventional excipients. [ABSTRACT FROM AUTHOR]

Polysorbates (PS) are added to biopharmaceutical formulations to stabilize proteins and monoclonal antibodies (mAbs) and to prevent aggregation, denaturation, and surface adsorption. Polysorbate analysis can be challenging because of their inherent complexity, polydispersity, and their presence in matrices containing high concentrations of proteins and other excipients such as sugars, amino acids, salts, and buffers. This instalment of "Biopharmaceutical Perspectives" provides an overview of different approaches for the qualitative and quantitative analysis of polysorbates, its impurities and degradants in raw material, intermediate dilutions, drug substance, and drug products. Various gas (GC) and liquid chromatography (LC) methods and accompanying detection techniques are briefly discussed and illustrated with results obtained at the authors' laboratory. [ABSTRACT FROM AUTHOR]

Background: Low solubility, poor permeability, and hepatic drug degradation are the primary factors responsible for the poor bioavailability issues of orally administered drugs. Ezetimibe, a biopharmaceutics classification system (BCS) Class II anti-cholesteremic drug, has a bioavailability between 35% and 65% due to its substantial intestinal and first-pass metabolism. Objectives: An alternative method for drug administration is to be attempted on an orally disintegrating Ezetimibe tablet to avoid low bioavailability, as mentioned earlier. Materials and Methods: The solubility issues of the drug were tackled by converting the drug into nano co-crystals using nicotinamide as a coformer utilizing the solvent anti-solvent method, followed by spray drying. The formulations were optimized using a custom experimental design. The optimum nano co-crystal formulation was converted into an orally disintegrating tablet using crospovidone as a super disintegrating agent and evaluated. Results: Nano co-crystals solubility was 0.030 to 0.049mg/mL. The release of the drug in a pH of 6.8 phosphate buffer was found to be 027.10±0.011 to 30.02±0.003%. Compatibility studies by FTIR confirm the absence of the drug's reaction with the excipients. X-ray, as well as DSC, indicated reduced Ezetimibe's crystalline nature. The disintegration time of ODT was marked down as 28 sec. ODT's in vitro release profile in PBS p 6.8 reveal a 20-fold increase in drug release compared to the pure drug. Conclusion: Therefore, ODTs containing nano co-crystals of Ezetimibe could provide a better alternative to improve solubility and the dissolution rate, which may enhance the bioavailability. [ABSTRACT FROM AUTHOR]

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With the rapid development of 3D printing technology, its application scope has involved various fields such as aerospace, the automobile industry, medical treatment, food and others. The US Food and Drug Administration (FDA) approved the release of "levetiracetam instant tablets," made with 3D printing technology. This means that 3D printing could be used to mass-produce drugs. This article reviews the principles, advantages, and challenges of 3D drug printing technologies: stereolithography, inkjet printing, powder-liquid bonding, and fused deposition, and looks forward to their future development in the preparation of solid preparations of medicine. With the continuous development of computer control, 3D printing industrialization and medicine excipients, and other technical fields, the application of 3D printing technology in the pharmaceutical industry will become more and more extensive. [ABSTRACT FROM AUTHOR]

Polylactic acids (PLAs) are synthetic polymers composed of repeating lactic acid subunits. For their good biocompatibility, PLAs have been approved and widely applied as pharmaceutical excipients and scaffold materials. Liquid chromatography-tandem mass spectrometry is a powerful analytical tool not only for pharmaceutical ingredients but also for pharmaceutical excipients. However, the characterization of PLAs presents particular problems for mass spectrometry techniques. In addition to their high molecular weights and wide polydispersity, multiple charging and various adductions are intrinsic features of electrospray ionization. In the present study, a strategy combining of differential mobility spectrometry (DMS), multiple ion monitoring (MIM) and in-source collision-induced dissociation (in source-CID) has been developed and applied to the characterization and quantitation of PLAs in rat plasma. First, PLAs will be fragmented into characteristic fragment ions under high declustering potential in the ionization source. The specific fragment ions are then screened twice by quadrupoles to ensure a high signal intensity and low interference for mass spectrometry detection. Subsequently, DMS technique has been applied to further reduce the background noise. The appropriately chosen surrogate specific precursor ions could be utilized for the qualitative and quantitative analysis of PLAs, which provided results with the advantages of low endogenous interference, sufficient sensitivity and selectivity for bioassay. The linearity of the method was evaluated over the concentration range 3–100 μg/mL (r2 = 0.996) for PLA 20,000. The LC-DMS-MIM coupled with in source-CID strategy may contribute to the pharmaceutical studies of PLAs and the possible prospects of other pharmaceutical excipients. [ABSTRACT FROM AUTHOR]

N -Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines. [ABSTRACT FROM AUTHOR]

In recent years, oncolytic viruses (OVs) have emerged as an effective means of treating cancer. OVs have multiple oncotherapeutic functions including specifically infecting and lysing tumor cells, initiating immune cell death, attacking and destroying tumor angiogenesis and triggering a broad bystander effect. Oncolytic viruses have been used in clinical trials and clinical treatment as drugs for cancer therapy, and as a result, oncolytic viruses are required to have long-term storage stability for clinical use. In the clinical application of oncolytic viruses, formulation design plays a decisive role in the stability of the virus. Therefore, this paper reviews the degradation factors and their degradation mechanisms (pH, thermal stress, freeze–thaw damage, surface adsorption, oxidation, etc.) faced by oncolytic viruses during storage, and it discusses how to rationally add excipients for the degradation mechanisms to achieve the purpose of maintaining the long-term stability of oncolytic viral activity. Finally, the formulation strategies for the long-term formulation stability of oncolytic viruses are discussed in terms of buffers, permeation agents, cryoprotectants, surfactants, free radical scavengers, and bulking agent based on virus degradation mechanisms. [ABSTRACT FROM AUTHOR]

Objective(s): Today, the non-covalent PEGylation methods of protein pharmaceuticals attract more attention and possess several advantages over the covalent approach. In the present study, Amino Acid-mPEGs (aa-mPEGs) were synthesized, and the human Growth Hormone (hGH) stability profile was assessed in their presence and absence. Materials and Methods: aa-mPEGs were synthesized with different amino acids (Trp, Glu, Arg, Cys, and Leu) and molecular weights of polymers (2 and 5 KDa). The aa-mPEGs were analyzed with different methods. The physical and structural stabilities of hGH were analyzed by SEC and CD spectroscopy methods. Physical stability was assayed at different temperatures within certain intervals. Molecular dynamics (MD) simulation was used to realize the possible mode of interaction between protein and aa-mPEGs. The cell-based method was used to evaluate the cytotoxicity. Results: HNMR and FTIR spectroscopy indicated that aa-mPEGs were successfully synthesized. hGH as a control group is known to be stable at 4 °C; a pronounced change in monomer degradation is observed when stored at 25 °C and 37 °C. hGH:Glu-mPEG 2 kDa with a molar ratio of 1:1 to the protein solution can significantly increase the physical stability. The CD spectroscopy method showed that the secondary structure of the protein was preserved during storage. aa-mPEGs did not show any cytotoxicity activities. The results of MD simulations were in line with experimental results. Conclusion: This paper showed that aa-mPEGs are potent excipients in decreasing the aggregation of hGH. Glu-mPEG exhibited the best-stabilizing properties in a harsh environment among other aa-mPEGs. [ABSTRACT FROM AUTHOR]

Currently available vaccines are safe, but, potentially, any vaccine can cause an allergic reaction and, albeit very rare, anaphylaxis can occur. Although its rarity, the precise diagnostic management of a suspected anaphylaxis postvaccination is of paramount importance due to the risk of a potentially serious reaction after re‐exposure, while a misdiagnosis might lead to an increase in the number of children that interrupt vaccinations resulting in an unjustifiably individual and collective risk of loss of protection against immune preventable diseases. In the light that most cases of suspected allergy to a vaccine are not effectively confirmed in up to 85% of the cases referred for an allergy evaluation, patients can continue the vaccination schedule with the same formulation and tolerance of the booster doses. The patient assessment has to be done by an expert in the vaccine field, usually an allergist or an immunologist depending on the country, to select subjects at risk of allergic reactions and to perform the correct procedures for vaccine hypersensitivity diagnosis and management, in order to guarantee safe immunization practices. The aim of this review is to provide a practical guidance for the safe management of allergic children undergoing immunization procedures. The guide is referred both to the evaluation of children who have previously experienced a suspected allergic reaction to a specific vaccine and their management in case of further booster doses, and to children allergic to a component of the vaccine to be administered. [ABSTRACT FROM AUTHOR]

This article investigates the impact of the interactions between polyurethane central venous catheters and solutions containing excipients used in cisplatin and paclitaxel formulations. Changes to the properties of catheters and the leaching of catheter additives into the infused solutions were studied while these solutions were infused cyclically for several months. Chemotherapy treatment was mimicked in vitro in compliance with hospital practices. The treatment cycle was repeated 10 times, using solutions containing only the excipients. After 10 treatment cycles, no physical or chemical degradation of the catheter was observed. Mechanical performances were stable, but surface modifications occurred, causing the surface to become more hydrophobic. A loss in polyurethane antioxidant amount was observed in part due to a leaching phenomenon. [ABSTRACT FROM AUTHOR]

Excipients, considered "inactive ingredients," are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant K d values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.

Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R-N=N-R') dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.

The rising incidence of antibiotic-resistant lung infections has instigated a much-needed search for new therapeutic strategies. One proposed strategy is the use of exogenous surfactants to deliver antimicrobial peptides (AMPs), like CATH-2, to infected regions of the lung. CATH-2 can kill bacteria through a diverse range of antibacterial pathways and exogenous surfactant can improve pulmonary drug distribution. Unfortunately, mixing AMPs with commercially available exogenous surfactants has been shown to negatively impact their antimicrobial function. It was hypothesized that the phosphatidylglycerol component of surfactant was inhibiting AMP function and that an exogenous surfactant, with a reduced phosphatidylglycerol composition would increase peptide mediated killing at a distal site. To better understand how surfactant lipids interacted with CATH-2 and affected its function, isothermal titration calorimetry and solid-state nuclear magnetic resonance spectroscopy as well as bacterial killing curves against Pseudomonas aeruginosa were utilized. Additionally, the wet bridge transfer system was used to evaluate surfactant spreading and peptide transport. Phosphatidylglycerol was the only surfactant lipid to significantly inhibit CATH-2 function, showing a stronger electrostatic interaction with the peptide than other lipids. Although diluting the phosphatidylglycerol content in an existing surfactant, through the addition of other lipids, significantly improved peptide function and distal killing, it also reduced surfactant spreading. A synthetic phosphatidylglycerol-free surfactant however, was shown to further improve CATH-2 delivery and function at a remote site. Based on these in vitro experiments synthetic phosphatidylglycerol-free surfactants seem optimal for delivering AMPs to the lung.

Mechanistic-understanding-based selection of excipients may improve formulation development strategies for generic drug products and potentially accelerate their approval. Our study aimed at investigating the effects of molecular excipients present in orally administered FDA-approved drug products on the intestinal efflux transporter, BCRP (ABCG2), which plays a critical role in drug absorption with potential implications on drug safety and efficacy. We determined the interactions of 136 oral molecular excipients with BCRP in isolated membrane vesicles and identified 26 excipients as BCRP inhibitors with IC50 values less than 5 μM using 3H-cholecystokinin octapeptide (3H-CCK8). These BCRP inhibitors belonged to three functional categories of excipients: dyes, surfactants, and flavoring agents. Compared with noninhibitors, BCRP inhibitors had significantly higher molecular weights and SLogP values. The inhibitory effects of excipients identified in membrane vesicles were also evaluated in BCRP-overexpressing HEK293 cells at similar concentrations. Only 1 of the 26 inhibitors of BCRP identified in vesicles inhibited BCRP-mediated 3H-oxypurinol uptake by more than 50%, consistent with the notion that BCRP inhibition depends on transmembrane or intracellular availability of the inhibitors. Collectively, the results of this study provide new information on excipient selection during the development of drug products with active pharmaceutical ingredients that are BCRP substrates.

Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.

Indonesian Halal Product Assurance Law No. 33 of 2014 states all products circulating in Indonesia must be halal-certified, including pharmaceuticals. Banana peel waste has the potential to produce pectin compounds as pharmaceutical excipients. This study is aimed at determining the characteristics of banana peel pectin as a potential halal pharmaceutical excipient. It has involved qualitative tests and established characteristics of extract pectin by organoleptic test, acidity (pH) test, solubility, equivalent weight, methoxyl concentration, galacturonic acid concentration, esterification degree, moisture content, and ash content. The yield of pectin produced was 17.19%. The qualitative test showed positive pectin, the characteristics of a white powder that is slightly ash, odorless, has a pH of 6.02, is soluble in water, insoluble in ethanol 96%, has an equivalent weight of 5,000 mg, methoxyl concentration of 2.6%, galacturonic acid concentration of 73.92%, esterification degree of 20.19%, moisture content of 7.139% and ash content of 1.6%. Based on the characterization results, banana peel pectin is, by pectin quality standards, a pharmaceutical excipient, especially as a raw material for manufacturing capsule shells, thickeners, and coating and gelling agents.

Nano-silver technology for cosmetics preparation is quite popular in recent times because nano-silver is non-toxic and has good antibacterial properties used to create products for skin protection purposes. This study investigated the preparation of a cream product that brings a moisturizing effect with hyaluronic acid and antibacterial effects with nano-silver extracted from natural, environmentally friendly passion fruit peels. The product not only meets the market demand but also brings outstanding efficiency in the application of the antibacterial properties of nano-silver to users. This study investigates the excipient ingredients to prepare a complete formula cream containing nano-silver with antibacterial and skin moisturizing properties. The nano-silver lotion formula was developed by evaluating the ability of excipient emulsions including oil phase - water phase excipients, emulsifying excipients, excipients with moisturizing effect, and the ratio of nano-silver. After that, the cream was evaluated for sensory, pH, skin irritation, moisturizing ability, and antibacterial ability on some strains of bacteria. The study was success in preparing a moisturizer containing nano-silver synthesized from passion fruit peel extract, satisfying the properties of a cosmetic product and encouraging further research.

Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at their sites of application. Polymers are composed of multiple repeating units of high molecular mass components with attendant properties. Most synthetic polymers are non-biocompatible, expensive, and extremely inclined to deliver adverse impacts. Meanwhile, edible polymers obtained from natural sources have gained remarkable recognition for their promising use in modern medicine. Moreover, polymers derived from natural sources are generally preferred due to certain of their unique features such as abundant availability, biocompatibility, nontoxicity, economical, safe, and effective functions that fit the purpose. Polysaccharides including starch, cellulose, hemicellulose, pectin, and mucilage are identified as a major class of naturally obtained molecules that have a substantial role as functional polymers. This review summarizes the potential role of polysaccharides derived from vegetable sources such as adhesives, anticaking agents, binders, disintegrants, emulsifiers, film-framing agents, and thickeners. This is simply an opportunity to abandon synthetic excipients that hurt our bodies and think back to nature from where we originate.

In this paper, ten samples containing promestriene (PRMS) were investigated, namely the pure active pharmaceutical ingredient (API) and nine binary mixtures prepared with commonly used excipients in solid pharmaceutical formulations. The necessity of such study is represented by the fact that the physicochemical screening of PRMS is not reported in the literature. Also, as convergent arguments for the necessity of this study, it can be mentioned that on Romanian pharmaceutical market, promestriene containing formulations are no longer commercialized since 2015, creating health problems to a large category of patients. As such, this study can serve as a starting point for the adequate selection of ingredients used in magistral preparations, with increased stability and bioavailability. The study revealed that PRMS is compatible with all of the selected excipients, namely methyl 2-hydroxyethyl cellulose (tylose), methyl cellulose (MethocelTM), starch, mannitol, magnesium stearate, magnesium citrate, Talc, colloidal SiO2 (aerosil) and polyvinylpyrrolidone K-30 (PVPK30), as confirmed by universal attenuated total reflectance Fourier transform infrared (UATR-FTIR) spectroscopy, powder X-ray diffraction patterns and thermal analysis. [ABSTRACT FROM AUTHOR]

Scientists have been faced with the challenge of selecting the right solubilizing excipients for solubility enhancement of poorly water-soluble active pharmaceutical ingredients for decades. In this investigation, the purpose was to ease some of those challenges by developing a first-intent matrix for selecting solubilizing excipients that may potentially be used in an oral solid dosage formulation. This was accomplished by generating 2304 data points using high throughput experimentation to assess the impact of eleven commonly used formulation excipients, at varying levels, on the solubility enhancement of a weak acid (Ibuprofen), weak base (Cinnarizine), and non-ionizable (Griseofulvin) drug substance over a time span from 1 h to equilibrium in simulated gastrointestinal fluids (SGF, FaSSIF, FeSSIF) and water. The results indicate that the enhancement of drug concentrations by use of solubilizing excipients (surfactants and stabilizers) in oral solid dosage forms depends on the type, the amount of excipient, and the pH of the media. The importance of this work is that formulation scientists now have a new addition to the formulation development toolkit for selecting the right solubilizing excipients and amounts suitable for solubility enhancement based on the class of active pharmaceutical ingredients. This first-intent solubilizer selection approach for the different drug classes simplifies the early development process to enable acceleration to candidate selection, formulation design, and product development for first-time-in-human studies. [Display omitted] • Solubility of pharmaceutical compounds can be enhanced by the use of excipients. • HTE can build large data which produces accurate predictive models. • Statistical analysis of data gives insight to significant experimental factors. • Solubility in simulated body fluids provides accurate representation of in-situ. [ABSTRACT FROM AUTHOR]

The current global situation of nitrosamine contamination has expanded from angiotensin-II receptor blockers (ARBs) to wide range of medicines as the risk of contamination via the drug substances, formulation, manufacturing process, and packaging is possible for many drug products. The understanding of chemistry, toxicology, and root causes of nitrosamines are mandatory to effectively evaluate and mitigate the risks associated with the contaminated mutagen. Lessons learnt and scientific findings from previously identified root causes are good examples on how to perform effective risk assessments and establish control strategies. Addressing the risk of nitrosamine contamination in pharmaceuticals requires significant knowledge and considerable resources to collect the necessary information for risk evaluation. Examples of the resources required include a reliable laboratory facility, reference material, highly specific and sensitive instrumentation able handle trace levels of contamination, data management, and the most limited resource - time. Therefore, the supporting tools to assist with risk assessment e.g., shared databases for drug and excipients in concern, screening models for the determination of nitrosamine formation potential, and an in silico model to help with toxicity estimation, have proven to be beneficial to tackle the risk and concern of nitrosamine contamination in pharmaceuticals. [Display omitted] [ABSTRACT FROM AUTHOR]

While many reactive species are known to cause N -nitrosation, trace nitrite (NO 2 −), which may be present in several excipients, is a source of nitrosating agents in pharmaceutical formulations. In this study we have found that the salt form of NO 2 − can influence the favored nitrosation conditions and final amount of nitrosamine being formed. Using native levels of NO 2 −, most likely present as ammonium nitrite (NH 4 NO 2), in microcrystalline cellulose, we have determined the kinetics of nitrosamine formation in solid state with dimethylamine substrate present in metformin, used as model compound. It was found that the competing degradation of NH 4 NO 2 into N 2 and H 2 O limited the amount of nitrosamine formation to a great extent. Empirically modelling the kinetic data predicted reaching at maximum 1.6% conversion over a hypothetical 3-year shelf-life. These results also showed that using other sources of NO 2 − as spiking reagents, such as NaNO 2 , may lead to unrealistic worst-case situations when the main form of NO 2 − in the drug product (DP) under evaluation may be NH 4 NO 2. As well, measuring NO 2 − in freshly manufactured excipients containing NO 2 − potentially as NH 4 NO 2 may lead to biased high NO 2 − content, which is not representative of the actual amounts present at the time of DP manufacture. [Display omitted] [ABSTRACT FROM AUTHOR]

The occurrence of N -nitrosodialkylamines in active pharmaceutical ingredients (APIs) and drug products in the last years was a kind of eye opener with regard to quality of drugs. We became aware of the fact that quality control tests described in the international pharmacopoeias might not be sufficient. The N -nitrosodialkylamines found were neither so-called (structurally) related substances, nor residual solvents or heavy metals; hence they were not limited by a compendial test, but by the ICH guideline M7 of mutagenic impurities. Additionally, nitrosamine drug-substance-related impurities (NDSRIs) were detected, mostly within the process of risk assessment required by regulatory authorities. Here, the APIs containing a vulnerable amino moiety had reacted with nitrites being a contaminant of an excipient. This review deals with the formation, toxicity, and mitigation of NDSRISs. [Display omitted] [ABSTRACT FROM AUTHOR]

Viscosity control is essential for the manufacturing and delivery of concentrated therapeutic proteins. Limited availability of the precious protein-based drugs hinders the characterization and screening of the formulation conditions with new types or different combinations of excipients. In this work, a droplet-based microfluidic device with incorporated multiple particle tracking microrheology (MPT) is developed to quantify the effects of two excipients, arginine hydrochloride (ArgHCl) and caffeine, on the viscosity of concentrated bovine gamma globulin (BGG) dispersions at two different values of pH. The effectiveness of both ArgHCl and caffeine show dependence on the BGG concentration and solution pH. The data set with high compositional resolution provides useful information to guide formulation with multiple viscosity-reducing excipients and quantification appropriate to start elucidating the connection to protein-protein interaction mechanisms. Overall, this work has demonstrated that the developed microfluidic approach has the potential to effectively assess the impact of multiple excipients on the viscosity and provide data for computational methods to predict viscosity for high concentration protein formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Nitrosamine impurities may form during drug substance manufacturing processes. Here, we focus on nitrosamine impurity level growth in oral drug products during long term stability studies. Nitrosamine growth mechanisms in oral dosage forms are typically framed as due to nitrosating agents that can be formed in solutions of nitrous acid with a required pH value of around pH 5 or below. We strive in this work to bring awareness to pharmaceutical scientists that formaldehyde, common in oral dosage form excipients, has previously been shown in solution to catalyze the reaction between secondary amines and nitrite ion to give nitrosamine products. This mechanism operates at pH ∼6 and higher. We attempt to re-frame the solution work as relevant to pharmaceutical solid dosage forms. Recent examples of solid dosage form product recalls are used to demonstrate the formaldehyde catalyzed nitrosation pathway operating in the solid state. [ABSTRACT FROM AUTHOR]

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best. [ABSTRACT FROM AUTHOR]

Recently, attention has been drawn to microwave-assisted freeze-drying (MFD), as it drastically reduces the typically long drying times of biopharmaceuticals in conventional freeze-drying (CFD). Nevertheless, previously described prototype machines lack important attributes such as in-chamber freezing and stoppering, not allowing for the performance of representative vial freeze-drying processes. In this study, we present a new technical MFD setup, designed with GMP processes in mind. It is based on a standard lyophilizer equipped with flat semiconductor microwave modules. The idea was to enable the retrofitting of standard freeze-dryers with a microwave option, which would reduce the hurdles of implementation. We aimed to collect process data with respect to the speed, settings, and controllability of the MFD processes. Moreover, we studied the performance of six monoclonal antibody (mAb) formulations in terms of quality after drying and stability after storage for 6 months. We found drying processes to be drastically shortened and well controllable and observed no signs of plasma discharge. The characterization of the lyophilizates revealed an elegant cake appearance and remarkably good stability in the mAb after MFD. Furthermore, overall storage stability was good, even when residual moisture was increased due to high concentrations of glass-forming excipients. A direct comparison of stability data following MFD and CFD demonstrated similar stability profiles. We conclude that the new machine design is highly advantageous, enabling the fast-drying of excipient-dominated, low-concentrated mAb formulations in compliance with modern manufacturing technology. [ABSTRACT FROM AUTHOR]

Recently, non-covalent reactions have emerged as approaches to improve the physicochemical properties of active pharmaceutical ingredients (API), including antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). This review aimed to present and discuss the non-covalent reaction products of antibiotics, including salt and neutral multi-component solid forms, by framing their substituents and molar ratios, manufacturing techniques, characterization methods, benefits, potency changes, and toxicity, and is completed with an analysis of the development of computational models used in this field. Based on the data, NSAIDs are the most-developed drugs in multi-component system preparations, followed by antibiotics, i.e., antituberculosis and fluoroquinolones. They have reacted with inorganic elements, excipients, nutraceuticals, natural products, and other drugs. However, in terms of treatments for common infections, fluoroquinolones are more frequently used. Generally, NSAIDs are acquired on an over-the-counter basis, causing inappropriate medication. In addition, the pKa differences between the two groups of medicine offer the potential for them to react non-covalently. Hence, this review highlights fluoroquinolone–NSAID multi-component solid systems, which offer some benefits. These systems can increase patient compliance and promote the appropriate monitoring of drug usage; the dual drug multi-component solids have been proven to improve the physicochemical properties of one or both components, especially in terms of solubility and stability. In addition, some reports show an enhancement of the antibiotic activity of the products. However, it is important to consider the possibility of activity changes, interaction, and toxicity when using drug combinations. Hence, these aspects also are discussed in this review. Finally, we present computational modeling, which has been utilized broadly to support multi-component system designs, including coformer screening, preparation methods, and structural modeling, as well as to predict physicochemical properties, potency, and toxicity. This integrated review is expected to be useful for further antibiotic–NSAID multi-component system development. [ABSTRACT FROM AUTHOR]

A green, rapid, and simple RP-UPLC method was developed and optimized by full factorial design for the simultaneous separation of oseltamivir phosphate, daclatasivir dihydrochloride, and remdesivir, with dexamethasone as a co-administered drug. The separation was established on a UPLC column BEH C18 1.7 µm (2.1 × 100.0 mm) connected with a UPLC pre-column BEH 1.7 µm (2.1 × 5.0 mm) at 25 °C with an injection volume of 10 µL. The detector (PDA) was set at 239 nm. The mobile phase consisted of methanol and ammonium acetate (8.1818 mM) in a ratio of 75.7: 24.3 (v/v). The flow rate was set at 0.048 mL min−1. The overall separation time was 9.5 min. The retention times of oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir were 6.323 ± 0.145, 7.166 ± 0.036, 8.078 ± 0.124, and 8.572 ± 0.166 min (eight replicates), respectively. The proposed method demonstrated linearity in the ranges of 10.0–500.0 (ng mL−1) and 0.5–30.0 (µg mL−1) for oseltamivir phosphate, 50.0–5000.0 (ng mL−1) for dexamethasone, 25.0–1000.0 (ng mL−1) and 0.5–25.0 (µg mL−1) for daclatasvir dihydrochlorde, and 10.0–500.0 (ng mL−1) and 0.5–30.0 (µg mL−1) for remdesivir. The coefficients of determination (R2) were greater than 0.9999, with percentage recoveries greater than 99.5% for each drug. The limits of quantitation were 6.4, 1.8, 7.8, and 1.6 ng mL−1, and the limits of detection were 1.9, 0.5, 2.0, and 0.5 ng mL−1 for oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir, respectively. The proposed method was highly precise, as indicated by the low percentage of relative standard deviation values of less than 1.2% for each drug. The average content and uniformity of dosage units in the studied drugs' dosage forms were determined. The average contents of oseltamivir phosphate, dexamethasone, daclatasivir dihydrochloride, and remdesivir were nearly 93%, 102%, 99%, and 95%, respectively, while the uniformity of dosage unit values were nearly 92%, 102%, 101%, and 97%. Two novel methods were established in this work. The first method was used to assess the stability of standard solutions. This novel method was based on the slope of regression equations. The second was to evaluate the excipient's interference using an innovative instrumental standard addition method. The novel instrumental standard addition method was performed using the UPLC instrument program. It was more accurate, sensitive, time-saving, economical, and eco-friendly than the classic standard addition method. The results showed that the proposed method can estimate the tested drugs' concentrations without interference from their dosage form excipients. According to the Eco-score (more than 75), the Green Analytical Procedure Index (GAPI), and the AGREE criteria (total score of 0.77), the suggested method was considered eco-friendly. [ABSTRACT FROM AUTHOR]

BACKGROUND: Two-drug regimens antiretroviral therapies are increasingly prescribed to HIV patients, as they are recommended by international guidelines, and they show an excellent efficacy, safety, and tolerability profile. Regimens administered as single tablets (STRs) are usually preferred by patients and they are associated with higher adherence. CASE REPORT: We report two cases of drug-induced hypersensitivity (DIH) that occurred after switching from dolutegravir (DTG) plus rilpivirine (RPV) in separate pills to a fixed dose combination containing the same molecules (DTG/RPV; Juluca®). Following the DIH event, DTG/RPV coformulation was discontinued. At symptomatic resolution, they continued to receive DTG plus RPV in separate pills uneventfully. The component present only in the DTG/RPV coformulation was iron oxide red (E172), contained in the film-coating. Iron oxide red is an approved colorant, used as drug excipient. Patch test with DTG/RV coformulation performed several months after the DIH event was negative. Drug allergy to excipients remains underappreciated and underreported and frequently leads to inappropriate medication discontinuation. CONCLUSION: Our case underscores the role of meticulous medication allergy history in differentiating true medication allergy from excipient allergy. This observation may be useful in the era of antiretroviral simplification to two-drug regimens. [ABSTRACT FROM AUTHOR]

Three different works combine to form a HF-3 dosage form, which is best on the basis of drug diffusion, in-vitro mucoadhesion and viscosity high solubility and, ease to use with adhesive nature over the skin, all three advantages are a must whenever we talk about the dermal formulation. The same happens with the drug amikacin, whose stability with minor solubility enhanced by the solid dispersion formation and encapsulated inside the vesicles called niosomes for sustained release and easy to adhere over the wound surface and finally, niosomes are encapsulated in hydrogels which provides the adhesive nature with easy to apply surety, at the same time it is able to provide a cooling sensation with surety to cure the wound. Also, drug and excipients have no interaction with each other and are quite stable in all dosage forms. Lastly all niosomal and hydrogel formulation compare with each other and proof that NF-8 as niosomal preparation and HF-3 as hydrogel preparation are overall best formulation and selected on the basis of many evaluation parameters. Finally one can conclude that whenever we select an oral route for targeting wound, there is a problem face by patient-related with improper amount of drug reached to the selected area and dose-related side effects and lastly patients non-compliance with tablet, for all this type of problems we can use the drug to be apply over the wound directly and for this prepared formulation NF-3 is best among all other formulation in case when we want to decrease dose frequency, directly applicable procedure and easy to use, and did not want any dose-related side effects as very less amount of drug used which is directly apply over wound and lastly slow or sustained drug release with almost whole drug penetrate from the wound which further help in heal the wound in less time duration. [ABSTRACT FROM AUTHOR]

Self-emulsification is considered a formulation technique that has proven capacity to improve oral drug delivery of poorly soluble drugs by advancing both solubility and bioavailability. The capacity of these formulations to produce emulsions after moderate agitation and dilution by means of water phase addition provides a simplified method to improve delivery of lipophilic drugs, where prolonged drug dissolution in the aqueous environment of the gastro-intestinal (GI) tract is known as the rate-limiting step rendering decreased drug absorption. Additionally, spontaneous emulsification has been reported as an innovative topical drug delivery system that enables successful crossing of mucus membranes as well as skin. The ease of formulation generated by the spontaneous emulsification technique itself is intriguing due to the simplified production procedure and unlimited upscaling possibilities. However, spontaneous emulsification depends solely on selecting excipients that complement each other in order to create a vehicle aimed at optimizing drug delivery. If excipients are not compatible or unable to spontaneously transpire into emulsions once exposed to mild agitation, no self-emulsification will be achieved. Therefore, the generalized view of excipients as inert bystanders facilitating delivery of an active compound cannot be accepted when selecting excipients needed to produce self-emulsifying drug delivery systems (SEDDSs). Hence, this review describes the excipients needed to generate dermal SEDDSs as well as self-double-emulsifying drug delivery systems (SDEDDSs); how to consider combinations that complement the incorporated drug(s); and an overview of using natural excipients as thickening agents and skin penetration enhancers. [ABSTRACT FROM AUTHOR]