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Structures of L-Arginine, L-Arginine Monohydrochloride, L-Histidine, L-Histidine Hydrochloride Monohydrate, L-Lysine and L-Lysine Monohydrochloride.
Source publication
Ion pairing is a potential strategy used to increase the partition and permeation of ionisable drug molecules. This work outlines the process of identifying, selecting and testing potential counter ions for diclofenac (DF). Three screening criteria were considered in the initial selection process. The first, toxicity, was used to eliminate counter...
Contexts in source publication
Context 1
... basic amino acids L-Arginine, L-Histidine, L-Lysine and their salts (Fig. 2), were selected as the potential counter ions. With reference to toxicity, the amino acids and their salts are generally recognised as safe (GRAS) when used as food additives by the FDA (Office of the Federal Register National Archives and Records Administration, 2011). They have also been used as cosmetic ingredients according to ...
Context 2
... was then washed three times using low pH (0.0001 M) HCl solution that had been maintained at a temperature of ±8 • C. This was followed by drying using a desiccator for 24 h. Confirmation that the product, DF, had been synthesised from DNa, was obtained by use of 1 H NMR. The appearance of a broad peak at approximately 12-13 ppm, as shown in Fig. S2, indicated the protonation of the carboxylic acid species, confirming free acid formation. The 1 H NMR spectrum of DNa, with no peak in the same area is shown in Fig. ...
Citations
... According to the result shown in Figure 5c, the incorporation of organic amines only slightly increased the drug release from the hydrogel. Therefore, the main cause of their enhancement effect would be attributed to their formation of ion pairs with the drug, which had been widely identified as a potential approach to improve the skin penetration of acidic or basic drugs with high lipophilicity [41,42]. The counter ions could electrostatically interact with the ionized AA, enabling the 'neutral' ion pair easier to partition from aqueous bases into an organic stratum corneum layer [41]. ...
... Therefore, the main cause of their enhancement effect would be attributed to their formation of ion pairs with the drug, which had been widely identified as a potential approach to improve the skin penetration of acidic or basic drugs with high lipophilicity [41,42]. The counter ions could electrostatically interact with the ionized AA, enabling the 'neutral' ion pair easier to partition from aqueous bases into an organic stratum corneum layer [41]. The obvious enhancement effect of NMP and ETA on skin penetration in the stratum corneum was presumably due to the hydrogen-bond forming ability of NMP and ETA, which could facilitate their interaction and drug miscibility with the stratum corneum [43]. ...
Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods. Four kinds of hydrogel bases were selected to prepare the AA hydrogel, in which different organic amines and chemical enhancers were incorporated in combination with microneedle pretreatment. The results showed that AA had good release profiles in the presence of hyaluronic acid as the hydrogel base and organic amines as the counter-ions. Diethylamine and Span 80 could promote drug penetration into the skin, and pretreatment with microneedles could further increase the drug permeability. In conclusion, the optimized hyaluronic acid hydrogel has great potential for use in the topical delivery of AA, and its penetration via the skin can be further improved by different pharmaceutical approaches.
Diclofenac (DF) is well established as a topical treatment option for conditions such as osteoarthritis. In investigating novel DF ion pairs for topical delivery, studies to determine the impact of various amino acids on the distribution of DF between octanol and aqueous environments were conducted. These studies identified the amino acid l-histidine hydrochloride monohydrate (LHSS) as an ion pair candidate for diclofenac sodium (DNa). Preliminary porcine skin permeation studies indicated that the addition of LHSS to DNa solutions increased the amount of DF that permeated through porcine skin. With increasing amounts of LHSS added, greater amounts of DF precipitated out of solution. In the present work, the solubility of DNa in various solvents was assessed, with the intention of identifying solvents in which DNa was most soluble. Binary systems comprising water and selected solvents were tested for both miscibility and the solubility of DNa and LHSS. The model system selected to evaluate novel ion pair formulations using porcine skin in vitro permeation studies under finite dose (10 μL) conditions comprised Transcutol® (TC) and water. The tested formulations contained DNa at concentrations of 5, 7.5 and 10 mg mL⁻¹. Higher LHSS concentrations were possible when the DNa concentrations were lower, and ranged from 10–25 mg mL⁻¹. However, increasing the DNa concentration to 10 mg mL⁻¹, without adding LHSS, resulted in a significant reduction in the amount of DF that partitioned and permeated, relative to formulations that contained either 5 mg mL⁻¹ DNa in combination with LHSS (at 12.5 or 25 mg mL⁻¹), or 7.5 mg mL⁻¹ DNa together with 12.5 mg mL⁻¹ LHSS. The current work confirms previous investigations, suggesting that the addition of LHSS to DNa in a formulation may increase the partition and permeation of DF.
Objectives:
To develop and evaluate a novel human stratum corneum (SC) mimetic phospholipid vesicle-based permeation assay (PVPASC) model for in vitro permeation studies.
Significance:
Due to the increasing restrictions on the use of human and animal skins, artificial skin models have attracted substantial interest in pharmaceuticals and cosmetic industries. In this study, a modified PVPASC model containing both SC lipids and proteins was developed.
Methods:
The PVPASC model was optimized by altering the lipid composition and adding keratin in the formulation of large liposomes. The barrier properties were monitored by measuring the electrical resistance (ER) and permeability of Rhodamine B (RB). The modified PVPASC model was characterized in terms of the surface topography, solvent influence and storage stability. The permeation studies of the active components in Compound Nanxing Zhitong Plaster (CNZP) were performed to examine the capability of PVPASC in the application of skin penetration.
Results:
The ER and Papp values of RB obtained from the optimized PVPASC model indicated a similar barrier property to porcine ear skin. Scanning electron microscope analysis demonstrated a mimic 'brick-and-mortar' structure. The PVPASC model can be stored for three weeks at -20 °C, and withstand the presence of different receptor medium for 24 h. The permeation studies of the active components demonstrated a good correlation (r2 = 0.9136) of Papp values between the drugs' permeation through the PVPASC model and porcine ear skin.
Conclusion:
Keratin contained composite phospholipid vesicle-based permeation assay models have been proven to be potential skin tools in topical/transdermal permeation studies.
For permeation studies that use excised skin, experimental data may show variability associated with the use of biological tissues. As a consequence, achieving reproducible results and data interpretation may be challenging. The skin parallel artificial membrane permeability assay (skin PAMPA) model has been proposed as a high-throughput tool for predicting skin permeation of chemicals. A number of skin cleansing wipe formulations for the diaper area of infants contain 2-phenoxyethanol (PE) as a preservative and cetylpyridinium chloride (CPC) as a surfactant with antimicrobial activity. However, information regarding cutaneous absorption of PE and CPC in the scientific literatures is remarkably limited. The main aim of the present study was to assess the suitability of the skin PAMPA model for prediction of skin permeation of PE. A secondary aim was to investigate the influence of CPC on the dermal absorption of PE. PE (1% w/w) was prepared in two vehicles, namely propylene glycol (PG) and water-PG (WP). Permeability of PE was investigated in vitro using the skin PAMPA membrane, porcine skin and human skin under finite dose conditions. The highest permeation of PE was observed for the water-PG preparation with 0.2% w/w of CPC. This finding was consistently observed in the skin PAMPA model and in Franz cell studies using porcine skin and human skin. Permeation of CPC was not detected in the three permeation models. However, permeation of PE increased significantly (p<0.05) in the presence of CPC compared with formulations without CPC. When comparing the skin PAMPA data and the mammalian skin data for the cumulative amount of PE permeated, the r2 values for PAMPA-porcine skin and PAMPA-human skin were 0.84 and 0.89, respectively. The findings in this study demonstrate the capability of the skin PAMPA model to differentiate between various doses and formulations and are encouraging for further applications of this model as a high throughput screening tool in topical formulation development.
Topical and transdermal delivery has historically offered an attractive and non-invasive route for administration of medicines. However, human skin is known to be a remarkably good barrier to the permeation of substances. The majority of dermatological drug products have been reported to only deliver a portion of the total dose applied, often resulting in low drug bio-availability at the site of action inside the skin. This insufficient formulation performance, coupled with the fact that percutaneous delivery is heavily influenced by the innate physicochemical properties of the active, pose limitations on effective treatment and prevention of diseases by using solely topical formulations. Generally, it is known that the rate and the extent of drug delivery to and through the skin is highly dependent on the formulation components. This work highlights the importance of the vehicle for the design of efficacious skin products, discusses current limitations in dermal delivery and explores recent advances for overcoming these challenges. Novel materials with penetration enhancing properties and innovative formulation strategies are also explored, together with future perspectives and outlooks. The emphasis here is on studies focused on passive skin transport because of clinical limitations associated with disrupting the skin barrier by physical methods. This information is believed to aid in the design and optimization of dermatological drug products for topical and transdermal delivery of actives.
