Amoxicillin chewable tablets intended for pediatric use: formulation development, stability evaluation and taste assessment.

To cover the unpleasant taste of amoxicillin (250 mg), maize starch (baby food) and milk chocolate were co-formulated. The raw materials and the final formulations were characterized by means of Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared (FT-IR) spectroscopy. To evaluate the taste masking two different groups of volunteers were used, according to the Ethical Research Committee of the Aristotle University of Thessaloniki. The optimization of excipients' content in the tablet was determined by experimental design methodology (crossed D-optimal). Due to the matrix complexity, amoxicillin was extracted using liquid extraction and analyzed isocratically by HPLC. The developed chromatographic method was validated (%Recovery 98.7-101.3, %RSD = 1.3, LOD and LOQ 0.15 and 0.45 µg mL-1 respectively) according to the International Conference on Harmonization (ICH) guidelines. The physicochemical properties of the tablets were also examined demonstrating satisfactory quality characteristics (diameter: 15 mm, thickness: 6 mm, hardness <98 Newton, loss of mass <1.0%, disintegration time ∼25min). Additionally, dissolution (%Recovery >90) and in vitro digestion tests (%Recovery >95) were carried out. Stability experiments indicated that amoxicillin is stable in the prepared formulations for at least one year (%Recovery <91).

Spray Drying of Chitosan Acid Salts: Process Development, Scaling Up and Physicochemical Material Characterization.

We investigated a spray drying process for preparing water-soluble salts of high molecular weight chitosan (CH) intended for pharmaceutical excipient applications. CH was derived from chitin of marine lobster origin (Panulirus argus). The effects of organic acid (acetic or lactic acid) and the ratio (difference) of inlet/outlet air temperature (140/90 °C or 160/100 °C) on spray drying were studied. The yield of spray-dried CH salt powders ranged from 50% to 99% in laboratory and industrial-scale processes. The spray-dried dry powder of CH salts consisted of spherical agglomerated particles with an average diameter of 36.2 ± 7.0 µm (CH acetate) and 108.6 ± 11.5 µm (CH lactate). After dispersing the spray-dried CH salt powder samples in purified water, the mean particle sizes obtained for the CH acetate salts were 31.4 nm (batch A001), 33.0 nm (A002) and 44.2 nm (A003), and for the CH lactate salts 100.8 nm (batch L001), 103.2 nm (L002) and 121.8 nm (L003). The optimum process conditions for spray drying were found: an inlet air temperature of 160 ± 5 °C, an outlet temperature of 100 ± 5 °C and an atomizer disk rotational speed of 18,200 min-1. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) results confirmed the amorphous state of the CH salts. The 1H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectra of CH acetate and lactate salts verified that the spray drying process does not affect the polymer backbone. In conclusion, both laboratory and industrial-scale spray drying methods for preparing water-soluble acid salts of CH are reproducible, and the physicochemical properties of the corresponding CH acid salts are uniform.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Agarose Stearate-Carbomer940 as Stabilizer and Rheology Modifier for Surfactant-Free Cosmetic Formulations.

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer940 (CBM940) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer940 showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM940 network played an important role in SFC's stability. Oil content could reinforce the elastic characteristics of the AS-CBM940 matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings.

Development of Gelucire® 48/16 and TPGS Mixed Micelles and Its Pellet Formulation by Extrusion Spheronization Technique for Dissolution Rate Enhancement of Curcumin.

The oral bioavailability of curcumin is limited, attributed to its low solubility or dissolution and poor absorption. Herein, the study describes formulation of curcumin-loaded mixed micelles of Gelucire® 48/16 and TPGS for its dissolution rate enhancement. Curcumin was dispersed in these molten lipidic surfactants which was then adsorbed on carrier and formulated as pellets by extrusion spheronization. Critical micelle concentration (CMC) of binary mixture of Gelucire® 48/16 and TPGS was lower than their individual CMC demonstrating the synergistic behavior of mixture. Thermodynamic parameters like partition coefficient and Gibbs free energy of solubilization indicated that mixed micelles were more efficient than micelles of its individual components in curcumin solubilization. Dynamic light scattering (DLS) suggested slight increase in micellar size of mixed micelles than its components suggesting curcumin loading in mixed micelles. Fourier transform infrared spectroscopy (FTIR) revealed that phenolic hydroxyl group interacts with lipids which contribute to its enhanced solubility. Furthermore, the differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study indicated the conversion of crystalline curcumin into amorphous form. In the pellet formulation, Gelucire® 48/16 acted as a binder and eliminated the requirement of additional binder. Microcrystalline cellulose (MCC) forms wet mass and retards the release of curcumin from pellets. Increase in concentration of water-soluble diluent increased drug release. The optimized formulation released more than 90% drug and maintains supersaturation level of curcumin for 2 h. Thus, mixed micellar system was effective delivery system for curcumin while pellet formulation is an interesting formulation strategy consisting semi-solid lipids.

Lipophilic Salts and Lipid-Based Formulations: Enhancing the Oral Delivery of Octreotide.

PURPOSE: Successful oral peptide delivery faces two major hurdles: low enzymatic stability in the gastro-intestinal lumen and poor intestinal membrane permeability. While lipid-based formulations (LBF) have the potential to overcome these barriers, effective formulation of peptides remains challenging. Lipophilic salt (LS) technology can increase the apparent lipophilicity of peptides, making them more suitable for LBF. METHODS: As a model therapeutic peptide, octreotide (OCT) was converted to the docusate LS (OCT.DoS2), and compared to the commercial acetate salt (OCT.OAc2) in oral absorption studies and related in vitro studies, including parallel artificial membrane permeability assay (PAMPA), Caco-2, in situ intestine perfusion, and simulated digestion in vitro models. The in vivo oral absorption of OCT.DoS2 and OCT.OAc2 formulated in self-emulsifying drug delivery systems (SEDDS) was studied in rats. RESULTS: LS formulation improved the solubility and loading of OCT in LBF excipients and OCT.DoS2 in combination with SEDDS showed higher OCT absorption than the acetate comparator in the in vivo studies in rats. The Caco-2 and in situ intestine perfusion models indicated no increases in permeability for OCT.DoS2. However, the in vitro digestion studies showed reduced enzymatic degradation of OCT.DoS2 when formulated in the SEDDS formulations. Further in vitro dissociation and release studies suggest that the enhanced bioavailability of OCT from SEDDS-incorporating OCT.DoS2 is likely a result of higher partitioning into and prolonged retention within lipid colloid structures. CONCLUSION: The combination of LS and LBF enhanced the in vivo oral absorption of OCT primarily via the protective effect of LBF sheltering the peptide from gastrointestinal degradation.

Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants.

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.

Streamlining of the Powder Mixing Process based on a Segregation Test.

In direct compression of tablets, it is crucial to maintain content uniformity within acceptable margins, especially in formulations with low drug loading. To assure it, complex and multistep mixing processes are utilized in the industry. In this study, we suggest the use of a simple segregation test to evaluate mixing process performance and mixture segregation to produce tablets having satisfying content uniformity while keeping the process as simple and low cost as possible. Eventually, the formulation propensity to segregation can be evaluated using process analytical technology (PAT) to adjust the mixing process parameters to changing source drug properties. In this study, that approach was examined on a model drug with a broad batch-to-batch variability in particle size and shape. Excipients were chosen so that the resulting blend composition mimicked some marketed formulations. For each drug batch, two formulation blends were prepared through different preparation processes (one simple and one complex) and subsequently subjected to segregation tests. From those, segregation coefficients were obtained to compare segregation tendencies and homogeneity robustness between the drug batches and the blend preparation methods. The inter-particulate interactions were substantially influenced by the drug particle morphology and size and resulted in different segregation behavior. Based on these findings, a simple segregation test proved to be a useful tool for determining the suitability of different batches of the model drug to be used in a certain formulation. Moreover, for a particular batch A, the test revealed a potential for mixing process simplification and therefore process intensification and cost reduction.

Preparation and evaluation of vancomycin spray-dried powders for pulmonary delivery.

The aim of the current study was to achieve a dry powder formulation of vancomycin by spray drying whilst evaluating the effect of pH and excipient type and percentage used in formulation on particle characteristics and aerosolization performance. A D-optimal design was applied to optimize the formulation comprising vancomycin and two main excipient groups; a carbohydrate bulking agent (lactose, mannitol or trehalose) and a second excipient (hydroxypropyl beta-cyclodextrin or L-leucine) at pH 4 and 7. The physicochemical properties of particles (size, morphology, crystallinity state, residual moisture content), stability, and aerosolization characteristics were investigated. Using the combination of two excipients increased the fine particle fraction of powder emitted from an Aerolizer® device at a flow rate of 60 L/min. Hydroxypropyl beta-cyclodextrin showed more potential than L-leucine in aerosolization capabilities. Stability studies over 3 months of storage in 40 °C and 75% relative humidity suggested a good physical stability of the optimized formulation containing 17.39% hydroxypropyl beta-cyclodextrin along with 29.61% trehalose relative to the amount of drug at pH 4. Use of two excipients including trehalose and hydroxypropyl beta-cyclodextrin with a total weight ratio of 47% relative to the amount of drug is appropriate for the preparation of vancomycin dry powder formulation for inhalation.

Liqui-Tablet: the Innovative Oral Dosage Form Using the Newly Developed Liqui-Mass Technology.

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.

A Multi-variate Mathematical Model for Simulating the Granule Size Distribution in Roller Compaction-Milling Process.

Granule size distribution (GSD) is one of the critical quality attributes in the roller compaction (RC) process. Determination of GSD for newly developed pharmaceutical compounds with unknown ribbon breakage behaviors at the RC milling step requires a quantitative insight into process parameters and ribbon attributes. Despite its pivotal role in mapping the process operating conditions to achieve desired granule size, limited work has been presented in literature with a focus on RC-milling modeling. In this study, a multi-variate mathematical model is presented to simulate the full size-distribution of granulated ribbons as a function of ribbon mechanical properties. Experimental data with a lab-scale oscillating milling apparatus were generated using ribbons made of various powder compositions. Model parameters were determined by fitting it to experimental data sets. Parameters obtained from the first step were correlated to ribbon Young's modulus. The model was validated by predicting GSD of data that were excluded in model development step. Predictive capabilities of the developed model were further explored by simulating GSD profiles of a granulated pharmaceutical excipient obtained at three different conditions of a real-scale Gerteis RC system. While maintaining the milling operating conditions similar to the lab-scale apparatus (i.e., screen size and spacing, and low rotor speed), the proposed modeling approach successfully predicted the GSD of roller compacted MCC powder as the model compound. This model can be alternatively utilized in conjunction with an RC model in order to facilitate the process understanding to obtain granule attributes as part of Quality-by-Design paradigm.

Effect of coating excipients on chemical stability of active coated tablets.

The objective of this study was to understand the impact of coating excipients on the chemical stability of active pan coated peliglitazar, which was prone to acid as well as base-catalyzed degradation. Four different coating formulations containing either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) as a coating polymer and triacetin (glycerol triacetate) or polyethylene glycol (PEG) as a plasticizer/detackifier were used for coating of peliglitazar in a perforated pan coater. Tablets of one-milligram strength were manufactured by suspending the drug in the coating suspension and spray coating onto inert core tablets. The active coated tablets were placed on stability (40 °C/75% RH) in high-density polyethylene (HDPE) bottles in closed condition with desiccants or in open condition. Tablet samples were withdrawn and analyzed for degradants using a stability-indicating HPLC method. The overall stability for the film-forming polymer-plasticizer/detackifier combination showed the rank order: HPMC-triacetin > PVA-triacetin > HPMC-PEG > PVA-PEG. Higher stability of triacetin systems over PEG systems was attributed to lower solubility of peliglitazar in triacetin coating systems. For the same plasticizer/detackifier, higher stability of HPMC over PVA-based formulations was attributed to lower solubility and mobility of peliglitazar in HPMC compared with the PVA-based coating.

Synthesis, characterization and potential application of hydrophobically modified carrageenan derivatives as pharmaceutical excipients.

New amphiphilic derivatives of kappa-carrageenan (KC) were synthesized by hydrophobic modification with octyl chloride. Two different methods based on microwave and conventional heating were used. All KC derivatives (KCRs) were characterized by different techniques. The FT-IR and 1HNMR studies demonstrated that the octyl groups were effectively grafted onto KC backbone and confirmed that the derivative KCRMM, obtained by microwave heating, presented a higher degree of substitution (DS = 0.77) compared to KCRCM (0.45). The amphiphilic character investigation also revealed that KCRMM exhibited a lower critical aggregation concentration (CAC) value of 0.13% w/v than KCRCM (0.15%). Furthermore, KCRs greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. Unlike the conventional heating method, novel derivatives with a higher DS, greater amphiphilic character, and an improved emulsifying power were obtained by microwave-assisted synthesis. These derivatives could potentially be used in food, cosmetics, or as excipients in pharmaceutics.

Safe, swallowable and palatable paediatric mini-tablet formulations for a WHO model list of essential medicines for children compound - A promising starting point for future PUMA applications.

More than 10 years after the Paediatric Regulation came into place there is still a strong need for paediatric medicines for off-patent drug substances. Numerous compounds for which a paediatric formulation does not exist can be found on the WHO Model List of Essential Medicines for Children and in the EMA Inventory of the Needs for Paediatric Medicines. Many of these compounds are off patent, which offers the opportunity for obtaining marketing authorisations for paediatric use. The present study focused on the development of paediatric immediate-release mini-tablet formulations for furosemide. Essential formulation criteria included the use of excipients that are regarded as safe for children, the ease of manufacturing, a high dose flexibility, fast disintegration, a robust drug release and a good acceptability. Only excipients regarded as safe for use in children were used in formulation screening. Compressibility, tablet hardness, disintegration and palatability were the main screening parameters. Formulations with a hardness of  > 20 N, a disintegration time < 3 min (fast disintegration) and a good palatability were selected for mini-tablet production. Based on this pre-assessment two mini-tablet formulations with a furosemide drug load of 2.5 mg were developed. Both were easy to manufacture, had an appropriate hardness, a short disintegration time and met pharmacopoeial requirements with regard to content uniformity and physical testing. Biorelevant in vitro dissolution experiments mimicking different modes (with water or dosing vehicles) of administering age-appropriate furosemide doses to children of different age groups indicated a fast and robust drug release. Overall, the novel mini-tablet formulations present with an increased dose flexibility, excipient safety, swallowability and palatability and are thus a promising starting point for the development of solid oral dosage forms for drugs with paediatric therapeutic needs.

Formulating monoclonal antibodies as powders for reconstitution at high concentration using spray-drying: Trehalose/amino acid combinations as reconstitution time reducing and stability improving formulations.

To increase their stability, therapeutic (or monoclonal) antibodies (mAbs) are often formulated as solids by using a variety of drying techniques, e.g. freeze-drying, spray-drying, or spray freeze-drying. The addition of excipients is required to preserve stability of the protein during the drying process and subsequent storage of the resulting solid form. The addition of low molecular weight excipients, such as amino acids, to sugar based spray- and freeze-dried formulations has been suggested to improve the storage stability of proteins in the dried state. In this study sugars (sucrose, trehalose), amino acids (Gly, Ala, Pro, Ser, Val, Leu, Ile, Gln, His, Lys, Arg, Phe, Trp) and combinations thereof were investigated for their stabilizing effect during spray-drying and subsequent storage and for their reconstitution time reducing effect. Two IgG4 mAbs were used as model antibodies. From an initial screening study, basic and small neutral amino acids, in combination with a sugar, such as sucrose or trehalose, showed reconstitution time reducing and stabilizing properties. Arg in particular displayed excellent reconstitution and stability enhancing properties. Moreover, Arg was the only amino acid providing stabilizing properties comparable to sucrose or trehalose. Previous work by the authors described a statistically substantiated comparison between the three basic amino acids in a sugar containing formulation, albeit limited to a single concentration level [5]. Therefore, a follow-up design of experiments (DoE) study was performed to determine the optimum trehalose/amino acid content required for an optimal protein stability and reconstitution time and to compare the effects of two basic amino acids, Lys and Arg, to those of two neutral amino acids, Gly and Pro. The conducted DoE covered a wide range of trehalose (30-120 mM) and amino acid (50-150 mM) concentrations. The concentration of trehalose was found to be the main contributor to a reduction in reconstitution time and an increase in stability. Here we show that the addition of amino acids such as Gly, Pro, and Lys does not improve stability nor does it reduce the reconstitution time. Of the tested amino acids, only Arg showed a marked reduction in reconstitution time and improvement in stability compared to a trehalose. Moreover, the properties displayed by Arg could justify its application as the main stabilizer in spray-dried mAb formulations, eliminating the need for a sugar matrix altogether. But the weight ratio of stabilizer to protein was found the factor exerting the strongest overall influence on the formulation's reconstitution time and stability. More specifically, sufficient physical stability and an acceptable reconstitution time could be obtained with a protein to stabilizer weight ratio of at least 1:1.

N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite hybrid supramolecular hydrogels as drug delivery vehicles with antibacterial property and cytocompatibility.

The intrinsic fragility of hydroxyapatite (HAP) restricts its wider applications for local delivery of antibiotics. The composites formed by integrating HAP with hydrogels can improve the properties of HAP. However, these reported composites not only require tedious preparation and employ organic solvent and toxic reagents, but also hardly have inherent antimicrobial property. In this study, N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite (Fmoc-L-Phe/nHAP) hybrid supramolecular hydrogels with antibacterial property and cytocompatibility was prepared by integrating nHAP as reinforcement with Fmoc-L-Phe supramolecular hydrogels. The results showed that nHAP bounds in the chamber of the gel network and adheres to the fiber of Fmoc-L-Phe due to intermolecular interaction, remarkably improving the mechanical strength of Fmoc-L-Phe supramolecular hydrogels. The results of inhibition zone experiment and MTT experiment showed that the Fmoc-L-Phe/nHAP hybrid supramolecular hydrogels possess antimicrobial property and cytocompatibility. In vitro release experiment of chlorogenic acid (CGA) from the hybrid supramolecular hydrogels was performed. The study of the release kinetics indicated that the release behavior of CGA from the hybrid supramolecular hydrogels is following Weibull model and release mechanism involved Fickian diffusion and erosion of the surface of hydrogel matrix. The release of CGA shows a good inhibition effect on S. aureus. The results show that the Fmoc-L-Phe/nHAP hybrid hydrogels with antibacterial property and cytocompatibility have promising applications as drug delivery carrier. Due to the intrinsic fragility of hydroxyapatite (HAP), the properties of HAP could be improved by incorporation into hydrogels. However, these reported composites not only require tedious preparation and employ organic solvent and toxic reagents, but also hardly have inherent antimicrobial property. We prepared N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite (Fmoc-L-Phe/nHAP) hybrid supramolecular hydrogels by integrating nHAP as reinforcement with Fmoc-L-Phe supramolecular hydrogels. The results showed that nHAP bounds in the chamber of the gel network and adheres to the fiber of Fmoc-L-Phe due to intermolecular interaction, remarkably improving the mechanical strength of Fmoc-L-Phe supramolecular hydrogels. The results of inhibition zone experiment and MTT experiment showed that the Fmoc-L-Phe/nHAP hybrid supramolecular hydrogels possess antibacterial property and cytocompatibility. In vitro release experiment of chlorogenic acid (CGA) from the hybrid supramolecular hydrogels was performed. The study of the release kinetics indicated that the release behavior of CGA from the hybrid supramolecular hydrogels is following Weibull model and release mechanism involved Fickian diffusion and erosion of the surface of hydrogel matrix. The release of CGA shows a good inhibition effect on S. aureus. The results show that the Fmoc-L-Phe/nHAP hybrid hydrogels with antibacterial property and cytocompatibility have promising applications as drug delivery carrier.

The extraordinary transformation of traditional Chinese medicine: processing with liquid excipients.

Context: The Chinese medicinal materials originate from animals, plants, or minerals must undergo appropriate treatment before use as decoction pieces. Processing of Chinese medicines with liquid excipients is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces which are significantly different from the original form. During processing, significant changes occur in chemical constituents, which inevitably affects clinical efficacy. At present, the liquid materials in processing mainly involve wine, vinegar, honey, saline water, ginger juice, herbal juice, etc.Objective: This review introduces the typical methods of liquid excipients processing, summarizes the influence on chemical composition, pharmacological efficacy, and expounds the ways and mechanisms of liquid excipients to change the properties of drugs, enhance the efficacy, eliminate or reduce toxicity and adverse reaction.Methods: English and Chinese literature from 1986 to 2020 was collected from databases including Web of Science, PubMed, Elsevier, Chinese Pharmacopoeia 2015, and CNKI (Chinese). Liquid excipients, processing, pharmacological effects, synergism, chemical constitution, traditional Chinese medicine (TCM) were used as the key words.Results: Liquid excipients play a key role in the application of TCM. Processing with proper liquid excipients can change the content of toxic or active components by physical or chemical transformation, decrease or increase drug dissolution, alter drug pharmacokinetics, or exert their own pharmacological effects. Thus, processing with liquid excipients is essential to ensure the safety and efficacy of TCM in clinic.Conclusion: This article could be helpful for researchers who are interested in traditional Chinese herbs processed with liquid excipients.

Sulfobutylether-ß-cyclodextrin/5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine nanoassemblies with sustained antimicrobial phototherapeutic action.

Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-ßCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT. Spherical nanoassemblies of about 360 nm based on CAPTISOL®/TMPyP supramolecular complexes with 1:1 stoichiometry and apparent equilibrium binding constant (Kb â‰… 1.32 × 105 M-1) were prepared with entrapment efficiency of â‰… 100% by simple mixing in aqueous media and freeze-drying. These systems have been characterized by complementary spectroscopy and microscopy techniques. Time resolved fluorescence pointed out the strong interaction of porphyrin monomer within nanoassemblies (τ2 â‰… 11 ns with an amount of ca 90%) and scarce self-aggregation of porphyrins have been observed. Singlet oxygen comparative determination (Ï•Δ CAPTISOL®/TMPyP = 0.58) assessed their photodynamic potential. Release and photostability studies have been carried out under physiological conditions pointing out the role of CAPTISOL® to sustain porphyrin release for more than 2 weeks and to protect PS from photodegradation. Finally, photoantimicrobial activity of nanoassemblies vs free porphyrin have been investigated against Gram-negative P. aeruginosa, E. coli and Gram-positive S. aureus. The proposed nanosystems were able to photokill both Gram-positive and -negative bacterial cells similarly to TMPyP at MBC90 = 6 µM of TMPyP and at 42 J/cm2 light dose. However, with respect to the less selective free TMPyP in biological sites, nanoassemblies exhibit sustained release properties and a higher photostability thus optimizing the PDT effect at the site of action. These results can open routes for in vivo translational studies on nano(photo)drugs and nanotheranostics based on less expensive formulations of CD and PS.

Influence of interparticle structuring on the surface energetics of a binary powder system.

The structuring of component particles in binary compositions affects the solid-solid interfacial properties. This work reports the effect of interparticle interactions in binary powder compositions of D-Mannitol and glass beads through the heterogeneity data obtained from Finite Dilution Inverse Gas Chromatography (FD-IGC). Three different scenarios viz. structured, random and segregated systems of the binary powder composition were considered for the analysis in the IGC column. Binary mixtures with large size disparity between the components produced structured mixtures exhibiting a guest-host type of interactions and energetic homogeneity irrespective of the energetics of the finer component. Random and segregated systems revealed a heterogeneous trend in the data indicating preferential probing of the active sites of the composition, particularly at the lower probe coverages. The results demonstrate that in the multicomponent binary systems the surface energetics is influenced by the solid-solid interfaces and structuring of the component particles within the mix i.e., the surface energy analysis could reveal a mixing behavior in powders. Furthermore, an adsorption energy distribution model based on Boltzmann statistics and simulation fitting approach was employed to deconvolute the distribution of the changing energy landscape of the binary mixtures.

A novel approach to avoid capping and/or lamination by application of external lower punch vibration.

Capping as well as lamination are two common problems, which affect the resulting product quality of the tablet. Usually, capping and lamination occur during or after tablet manufacturing, and may therefore influence follow-up processes such as the coating. In this context, there is an urgent need for approaches to overcome the occurrences of capping and lamination. In the present study, a novel lower punch vibration technique was used to decrease the capping or lamination tendency of different powder formulations. Different microcrystalline cellulose types, as well as an API (acetaminophen), were selected as model powders. The powders were investigated regarding their powder flow, density, particle morphology, and surface area. Moreover, the manufactured tablets were characterized regarding their tablet weight, tensile strength, and capping or lamination indices. It was shown that the capping or lamination tendency was strongly affected by the physical powder properties, the formulation composition, and the adjusted turret speed. In addition, the application of externally applied lower punch vibration led to a pronounced decrease of the capping or lamination tendency and improved mechanical stability of the manufactured tablets.