190 research outputs found
Effect of amino acid-based surfactants on Caco-2 cell permeability of macromolecular drugs
No full textBackgroundsSurfactants are amphiphilic molecules of large interest in the pharmaceutical field. An
interesting technological application of surfactants is their use as permeability enhancers. At this end,
different amphiphilic compounds have been investigated both iAimsThe aim of the study was to
evaluate the effect of N-acyl serine and N-acyl alanine on Caco-2 cell monolayer permeability of
fluorescein isothiocyanate–dextran 4kDa (as model for macromolecular drug) in comparison to
SDS, a well-knMethodsN-acyl serine and N-acyl alanine, with different lengths of the hydrocarbon
chains (from C10 to C16) were synthesized. Transepithelial electrical resistance (TEER) at not-toxic
concentrations (100% cell viability) across Caco-2 cell monoResultsA decrease in TEER was observed
after exposure to N-acyl surfactants. Particularly, the decrease in TEER was proportional to the length of
the hydrocarbon chain, reaching values comparable to SDS, when C16 derivatives were tested.
Permeability studies refSummary/ConclusionThis study demonstrated that N-acyl serine and N-acyl
alanine can act as permeability enhancers for oral absorption of macromolecular drugs
Dextran and its potential use as tablet excipient
No full textDextrans are a class of carbohydrate polymers extensively applied in pharmaceutical applications, particularly as drug conjugate macromolecular carriers or drug delivery systems. These polysaccharides improve the stability of the therapeutics enabling also the control of their release, via either the parenteral and or oral routes. In the latter case, due to their gel forming ability they may have potential as hydrophilic matrix tablets for sustained drug release.
In this paper, we investigated the behaviour of different molecular weight (1, 40, 500 and 2300 kDa) dextrans as tabletting excipients. Powder particle size and hygroscopic studies have been reported, together with tabletability, tablet stability and tablet swelling. Moreover we use tramadol as model compound to evaluate the ability of dextrans to control drug dissolution. The results suggest that dextrans with lower molecular weights may be a promising excipient to be used as filler for immediate release tablets, due to their good tabletability and fast dissolution rate, while dextrans with higher molecular weights could be an efficient disintegrant due to their swelling ability
PEGylated polylactide (PLA) and poly (lactic-co-glycolic acid) (PLGA) copolymers for the design of drug delivery systems
No full textBackground: PEGylated polylactide (PLA) and poly (lactic-co-glycolic acid) (PLGA) copolymers are biodegradable polyesters, widely employed in the last decades for the design of drug delivery systems such as polymeric hydrogels and nanocarriers (e.g. micelles and nanoparticles). The coupling with polyethylene glycol (PEG) offers some advantages with the respect to PLA and PLGA, including a higher hydrophilicity and a prolonged retention time for nanoparticulate systems, as well as the possibility of preparing thermoresponsive hydrogels. A large variety of pharmacologically active-compounds (small molecules, natural compounds or biomolecules such as proteins, peptides, oligonucleotides) has been formulated and delivered through PEGylated PLA or PLGA copolymers. Due to the high number of papers recently published about the use of these biodegradable copolymers in drug delivery, PEGylated PLA or PLGA copolymers are being still attractive. Their potential applications have been also broadened by the developing of ligand-functionalized copolymers, enabling an “active drug targeting” for nanoparticulate systems. Area covered: The present review summarizes the recent advances in drug delivery systems based on PEGylated PLA or PLGA copolymers, focusing on self-assembled micelles and thermoresponsive hydrogels as well as nanoparticles. A particular consideration has been given to functionalized PEGylated PLA/PLGA nanoparticles for active drug delivery. Expert opinion: Further advances in the design of PEGylated PLA/PLGA delivery systems will be beneficial for an improved drug release and targeting in the light of novel personalised therapeutic strategies. © 2019, The Korean Society of Pharmaceutical Sciences and Technology
Acoustic spectroscopy: A powerful analytical method for the pharmaceutical field?
No full textAcoustics is one of the emerging technologies developed to minimize processing, maximize quality and ensure the safety of pharmaceutical, food and chemical products. The operating principle of acoustic spectroscopy is the measurement of the ultrasound pulse intensity and phase after its propagation through a sample. The main goal of this technique is to characterise concentrated colloidal dispersions without dilution, in such a way as to be able to analyse non-transparent and even highly structured systems. This review presents the state of the art of ultrasound-based techniques in pharmaceutical pre-formulation and formulation steps, showing their potential, applicability and limits. It reports in a simplified version the theory behind acoustic spectroscopy, describes the most common equipment on the market, and finally overviews different studies performed on systems and materials used in the pharmaceutical or related fields
Effects of thermal and physical treatments on donkey milk nutritional properties
No full textDonkey milk (DM) may be considered a good and safe replacer to other kinds of milk for patients affected by cow's milk protein allergy (CMPA), which is an abnormal immunological reaction to cow milk proteins, resulting in immediate IgE-mediated reactions [1]. An important attribute of DM is its chemical resemblance to human milk especially regarding the lactose and the protein content, and also mineral composition [2]. The hypoallergenic properties of DM are due to the low content of αs1-and β-caseins and the presence of αs2- and κ-caseins trace levels [3]. Furthermore, DM is characterized by the presence of bioactive proteins (lysozyme, lactoferrin, -lactalbumin) which have important nutraceutical properties, and by a high content of vitamin C. However, the main problem on the use of DM is its poor availability (responsible of the high cost per liter of this food) which is limited to few months per year, because the ass’s fertility is strictly connected with photoperiod. At this purpose, it is important to find valid long-term storage conditions that keep unaltered the nutraceutical properties of this milk. In this work, the whey protein fraction (normally used to study the impact of a thermal treatment on milk) and the vitamin C content has been analyzed after some thermal treatments on donkey milk such as freezing (-20°C), lyophilization (freeze-drying), and spray-drying technique. Three representative whey proteins, β-lactoglobulin, α-lactalbumin, and lysozyme, from fresh DM, frozen milk (-20°C) and both reconstituted freeze-dried and spray-dried DM have been analyzed by RP-HPLC, dynamic light scattering analyses and differential scanning microcalorimetry experiments. The enzymatic activity of lysozyme has been also performed since it can represent a valuable index of the nutritional quality of the processed milk. Results obtained were compared with those determined on fresh milk. RP-HPLC analyses revealed that the freeze-drying and spray-drying processes reduced significantly (P < 0.05) β-lactoglobulin concentration whereas lysozyme maintains 96% and 58% residual activity in the freeze-dried milk and spray-dried DM, respectively [4]. The content of α-lactalbumin was not affected by these two drying processes. Differential scanning microcalorimetry and dynamic light scattering analyses were performed to investigate the thermal behavior of lysozyme, β-lactoglobulin and α-lactalbumin from fresh, freeze-dried and spray-dried DM, revealing no effect on the thermal behavior of whey proteins. When DM is maintained at -20° for up to three months α-lactalbumin and β-lactoglobulin content resulted quite stable. The lysozyme activity, in fresh as well as in frozen milk, resulted to be 0.035 U/ml, indicating that the freezing and thawing out process do not affect the activity of this important enzyme. L-Ascorbic acid (vitamin C) can be used as a quality indicator in the production of several foods and derivatives such as wine, beer, milk, soft drinks and fruit juices. Fresh DM contains 57 mg of vitamin C per liter of milk. The freeze-drying process did not significantly affect the amount of vitamin C in DM but its content significantly decreased (P<0.01) after one, two and three months of storage at -20°C. In conclusion, the spray-drying process caused a significant decrease of DM lysozyme enzymatic activity and of β-lactoglobulin total amount, because of the high temperature to which milk is subjected during this treatment. Freeze-drying treatment demonstrated that the nutritional characteristics of DM remained basically unchanged if compared with fresh DM.
References
[1] Carroccio A, Cavataio F, Montalto G, D'Amico D, Alabrese L. Intolerance to hydrolysated cow's milk proteins in infants: Characteristics and dietary treatment. Clin Exp Allergy. 2000;30:1597-1603.
[2] Salimei E, Fantuz F, Coppola R, Chiofalo B, Polidori P, Varisco G. Composition and characteristics of ass's milk. Animal Research. 2004;53:67-68.
[3] Vincenzetti S, Polidori P, Mariani P, Cammertoni N, Fantuz F, Vita A. Donkey's milk protein fraction characterization. Food Chemistry. 2008;106:640-649.
[4] Vincenzetti S, Cecchi T, Perinelli DR, Pucciarelli S, Polzonetti V, Bonacucina G, Ariani A, Parrocchia L, Spera DM, Ferretti E, Vallesi P, Polidori P. Effects of freeze-drying and spray- drying on donkey milk volatile compounds and whey proteins stability. LWT - Food Sci Technol. 2018; 88: 189-195
Experimental factors affecting drug release from gel using VanKel (ENHANCER®) cells
No full textDissolution tests are quality control analyses routinely performed by pharmaceutical companies in order to assess the manufacturing process through the control of the reproducibility of the kinetic of the drug released from solid or semi-solid dosage forms. The European (8th Eu.Ph) and Italian Pharmacopoeia (FU XIII) report several dissolution test apparatus (type 1 to type 4) for different purposes, however some discrepancies remain about the use of the sample compartment for semi-solid dosage forms. VanKel Cell (Enhancer cell) is a PTFE volume–adjustable cell commonly used for in vitro release studies of semisolid formulations. However, even if this system has been widely used for research purpose in the last 20 years, a standardization of the method is still missing. The knowledge of the experimental factors influencing the dissolution test by using these cells is fundamental, especially in the case of their possible approval by the European Pharmacopoeia. Dissolution analyses were performed in a type-2 apparatus by using a 22% Poloxamer 407 gel, loaded with tramadol (25 mg/ml), as semi-solid formulation model. 2 g of the gel was placed inside a 4cm2 VanKel Cell mounting a membrane. Several parameters, as the position of gel loaded inside the cell, the speed and distance of the paddles from the cells and the thickness and the porosity of the membrane, have been investigated. Results from the dissolution experiments obtained at different conditions were analysed by calculating the dissolution efficiency (DE) and by fitting experimental data by the power law model. The statistical comparison revealed which are the most influencing parameters on the drug release from VanKel dissolution cells. A correct loading of the gel in the cell is fundamental in order to perform the release study. In addition, the thickness of the membrane and the speed of the paddles are important factors affecting drug release, contrarily to the distance of the paddle over cell compartment which was found not to influence the release profile. A slightly effect on the release profile was also observed with membranes at different porosity
Hydrogel containing mPEG-PLGA nanoparticles for the vaginal delivery of saquinavir mesylate against HIV infection
No full textSaquinavir mesylate (SQV) is a protease inhibitor commonly employed for the treatment of human immunodeficiency virus-1 infection. It is generally administered orally as tablets in combination with other antiviral drugs. Another promising route of administration can be represented by the vaginal one through topically applied formulations. This delivery can reduce the first-pass effect in the case of systemic drug adsorption or prevent HIV infection. We propose the formulation of a Carbopol® 974 (C974) hydrogel containing biodegradable mPEG-PL(L)GA nanoparticles (NPs) for the vaginal delivery of SQV, intended both as a prevention and a therapeutic strategy. mPEG-PL(L)GA NPs were incorporated into the C974 polymeric matrix, leading to a reduction of the hydrogel consistency dependent on NPs and C974 concentrations. Despite the moderate drug loading into NPs, the presence of the NPs had an impact on the in vitro release of the drug from the hydrogel at pH 5.5 using immersion cells. A higher amount of the drug was released, probably due to the effect of NPs in promoting the incorporation of the drug into the hydrogel at a high SQV dose. These findings can be useful for the development of topically applied hydrogels for SQV delivery, possibly having improved in vivo therapeutic outcomes
Enteral Delivery of Pravastatin Sodium Tablets: Effect of Compounding into a Liquid Form and Co-Administration of Enteral Nutrition
No full textBackground: Compounding solid oral dosage forms into liquid preparations is a common practice for administering drug therapy to patients with swallowing difficulties. This is particularly relevant for those on enteral nutrition, where factors such as the administration procedure and co-administration of enteral nutrition play crucial roles in effective drug delivery. Due to the limited studies focused on this practice, the impact of co-administered nutrition remains unclear. Methods: Pravastatin tablets were compounded into two liquid formulations and administered through three independent tubes for ten cycles. The drug amount was quantified upstream and downstream of the tubes both with and without different (fiber content) nutritional boluses. Results: The compounding procedure did not lower the drug amount with respect to the original tablets. However, when the liquid formulation was pumped through the tubes, a statistically significant reduction in the pravastatin administered (between 4.6% and 11.3%) was observed. The co-administration of different nutritional boluses or the compounding procedure did not affect the general results. Conclusions: Pravastatin loss appears unavoidable when administered via the enteral tube. Although, in this case, the loss was of limited clinical relevance, it is important not to underestimate this phenomenon, especially with drugs having a narrow therapeutic index
Exploring Immersion Coating as a Cost-Effective Method for Small-Scale Production of Enteric-Coated Gelatin Capsules
No full textThe coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production
Sodium lauryl sulfate as lubricant in tablets formulations: Is it worth?
No full textLubricants are excipients used in tablet formulations to reduce friction and adhesion forces within the die or on the punches surface during the manufacturing process. Despite these excipients are always required for the tablets production, their amount must be carefully evaluated since lubricants can negatively impact on me-chanical strength, disintegration and dissolution behavior of solid dosage forms. Alternative compounds have been suggested to overcome the issues of conventional lubricants and sodium lauryl sulfate (SDS) is one of the most promising one. Despite SDS has been object of several investigations, a definitive conclusion on its effec-tiveness cannot still be drawn. Particularly, its efficacy on tablets disaggregation and API dissolution is still unclear. Here, the effect of SDS on all the relevant features of tablets and tableting process has been evaluated on immediate release hydrophobic tablets formulations in comparison with conventional lubricants. The results of this investigation are quite outspoken: SDS has a low lubricant power while it determines only a limited improvement on tablets hardness. It greatly improves the tablets wettability but only on model formulations, the presence of superdisintegrants resets its effectiveness and any possible effect on tablets disaggregation. None of the tested formulations showed improvement on the API dissolution rate
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