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12 pages, 432 KiB

Open AccessArticle

Does the Vehicle Matter? Real-World Evidence on Adherence to Topical Treatment in Psoriasis

by Ana Teixeira, Maribel Teixeira, Vera Almeida, Rita Gaio, Tiago Torres, Sofia Magina, Cátia Cunha, José M. Sousa Lobo and Isabel F. Almeida

Pharmaceutics 2021, 13(10), 1539; https://doi.org/10.3390/pharmaceutics13101539 - 23 Sep 2021

Cited by 13 | Viewed by 2364

Abstract

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The [...] Read more.

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The adherence was evaluated in a sample of 102 psoriasis patients, followed for approximately 45 days. Adherence was calculated with a new combined methodology using a log and medication weights. The effect of the group formulation was evaluated using logistic regression models. A complex effect of the vehicle on adherence was found, mediated by the affected area. The adherence was significantly higher for patients applying gels and creams than for those using ointments, whenever the body area affected was extensive. The opposite was found when the affected area was small. Mechanical properties can partially explain the findings since gels and creams may be easier to apply. Patient beliefs and preferences regarding vehicles and their sensory attributes might also explain the results. It is noteworthy that adherence was strikingly low, with more than 75% non-adherent patients. This real-world evidence provides an insight for pharmaceutical industries and guidance for treatment prescription by physicians aiming to address the public health emergency of treatment non-adherence. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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19 pages, 2132 KiB

Open AccessArticle

Impact of Alkanediols on Stratum Corneum Lipids and Triamcinolone Acetonide Skin Penetration

by Melanie Sigg and Rolf Daniels

Pharmaceutics 2021, 13(9), 1451; https://doi.org/10.3390/pharmaceutics13091451 - 11 Sep 2021

Cited by 5 | Viewed by 2401

Abstract

Alkanediols are widely used as multifunctional ingredients in dermal formulations. In addition to their preservative effect, considering their possible impact on drug penetration is also essential for their use. In the present study, the influence of 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the [...] Read more.

Alkanediols are widely used as multifunctional ingredients in dermal formulations. In addition to their preservative effect, considering their possible impact on drug penetration is also essential for their use. In the present study, the influence of 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the skin penetration of triamcinolone acetonide from four different semisolid formulations was investigated. Furthermore, confocal Raman spectroscopy measurements were performed to examine the influence of the alkanediols on stratum corneum lipid content and order. Alkanediols were found to increase the penetration of triamcinolone acetonide. However, the extent depends strongly on the formulation used. In certain formulations, 1,2-pentanediol showed the highest effect, while in others the penetration-enhancing effect increased with the alkyl chain length of the alkanediol used. None of the tested alkanediols extracted lipids from the stratum corneum nor reduced its thickness. Notwithstanding the above, the longer-chained alkanediols cause the lipids to be converted to a more disordered state, which favors drug penetration. This behavior could not be detected for the shorter-chained alkanediols. Therefore, their penetration-enhancing effect is supposed to be related to an interaction with the hydrophilic regions of the stratum corneum. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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11 pages, 2842 KiB

Open AccessArticle

In Vitro and Clinical Safety Assessment of the Multiple W/O/W Emulsion Based on the Active Ingredients from Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L.

by Ugne Zlabiene, Juste Baranauskaite, Dalia M. Kopustinskiene and Jurga Bernatoniene

Pharmaceutics 2021, 13(5), 732; https://doi.org/10.3390/pharmaceutics13050732 - 16 May 2021

Cited by 4 | Viewed by 2543

Abstract

The multiple W/O/W emulsion supplemented with the extracts of Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L. was prepared in the study, its active compounds were determined by HPLC and its safety was evaluated in vitro by the means of reconstituted [...] Read more.

The multiple W/O/W emulsion supplemented with the extracts of Rosmarinus officinalis L., Avena sativa L. and Linum usitatissimum L. was prepared in the study, its active compounds were determined by HPLC and its safety was evaluated in vitro by the means of reconstituted human skin model EpiDerm™ for the assessment of its irritation, phototoxicity and early skin inflammation effects and by the 48 h human skin patch test for its skin irritation and allergenic potential. The microbiological challenge test of W/O/W emulsion was performed to ensure its preservation efficiency. The results showed that the W/O/W emulsion loaded with self-preserving plant-based bio-actives had no irritant potential, was not phototoxic and did not provoke skin inflammation or sensitization and thus could be used as a safe base for cosmetic products. Furthermore, our results demonstrate that the safety evaluation of cosmetic ingredients of natural or organic origin could be easily performed using reconstructed human skin model EpiDerm™ similar to the well-defined chemicals used in the cosmetics industry. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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14 pages, 2717 KiB

Open AccessArticle

Dermal Delivery of Niacinamide—In Vivo Studies

by Yanling Zhang, Chin-Ping Kung, Fotis Iliopoulos, Bruno C. Sil, Jonathan Hadgraft and Majella E. Lane

Pharmaceutics 2021, 13(5), 726; https://doi.org/10.3390/pharmaceutics13050726 - 14 May 2021

Cited by 13 | Viewed by 4398

Abstract

In vivo human studies are considered to be the “gold standard” when investigating (trans)dermal delivery of actives. Previously, we reported the effects of a range of vehicles on the delivery of niacinamide (NIA) using conventional Franz cell studies. In the present work, dermal [...] Read more.

In vivo human studies are considered to be the “gold standard” when investigating (trans)dermal delivery of actives. Previously, we reported the effects of a range of vehicles on the delivery of niacinamide (NIA) using conventional Franz cell studies. In the present work, dermal delivery of NIA was investigated in vivo in human subjects using confocal Raman spectroscopy (CRS) and tape stripping (TS). The vehicles investigated included propylene glycol (PG), Transcutol^® P (TC), binary combinations of PG with oleic acid (OA) or linolenic acid (LA) and a ternary system comprising of TC, caprylic/capric triglyceride (CCT) and dimethyl isosorbide (DMI). For the CRS studies, higher area under curve (AUC) values for NIA were observed for the PG:LA binary system compared with PG, TC and TC:CCT:DMI (p < 0.05). A very good correlation was found between the in vitro cumulative permeation of NIA and the AUC values from Raman intensity depth profiles, with a Pearson correlation coefficient (R²) of 0.84. In addition, an excellent correlation (R² = 0.97) was evident for the signal of the solvent PG and the active. CRS was also shown to discriminate between NIA in solution versus crystalline NIA. The findings confirm that CRS is emerging as a powerful approach for dermatopharmacokinetic studies of both actives and excipients in human. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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14 pages, 4074 KiB

Open AccessArticle

Investigations on Alkanediols as Alternative Preservatives in a Nonionic Hydrophilic Cream

by Melanie Sigg and Rolf Daniels

Pharmaceutics 2020, 12(11), 1117; https://doi.org/10.3390/pharmaceutics12111117 - 20 Nov 2020

Cited by 6 | Viewed by 2994

Abstract

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect [...] Read more.

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect of four different alkanediols, namely 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol, and 1,2-octanediol on the physical stability of a nonionic hydrophilic cream was investigated. Further, the incorporation of the alkanediols into lamellar structures of the cream was evaluated using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) measurements. The interaction with the mixed crystals of the cream was found to increase with raising alkyl chain length of the added alkanediol. As a result, consistency and stability of the cream are slightly impaired. A test for efficacy of antimicrobial preservation according to the European Pharmacopoeia (Ph.Eur.) revealed that the antimicrobial activity is directly linked to the length of the alkyl chain of the alkanediols. 2-Methyl-2,4-pentanediol differs from both findings. This compound has non-vicinal hydroxy groups which result in a reduced amphiphilicity compared to the others. Consequently, it has a smaller impact on the colloidal structure of the cream and shows a comparatively low antimicrobial activity. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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Review

Jump to: Research

19 pages, 1177 KiB

Open AccessReview

Film-Forming Systems for Dermal Drug Delivery

by Larissa Carine Pünnel and Dominique Jasmin Lunter

Pharmaceutics 2021, 13(7), 932; https://doi.org/10.3390/pharmaceutics13070932 - 23 Jun 2021

Cited by 33 | Viewed by 8807

Abstract

Film-forming formulations represent a novel form of sustained release dermatic products. They are applied to the skin as a liquid or semi-solid preparation. By evaporation of the volatile solvent on the skin, the polymer contained in the formulation forms a solid film. Various [...] Read more.

Film-forming formulations represent a novel form of sustained release dermatic products. They are applied to the skin as a liquid or semi-solid preparation. By evaporation of the volatile solvent on the skin, the polymer contained in the formulation forms a solid film. Various film-forming formulations were tested for their water and abrasion resistance and compared with conventional semi-solid formulations. Penetration and permeation studies of the formulations indicate a potential utility as transdermal therapeutic systems. They can be used as an alternative to patch systems to administer a variety of drugs in a topical way and may provide sustained release characteristics. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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31 pages, 3407 KiB

Open AccessReview

Ion Pairs for Transdermal and Dermal Drug Delivery: A Review

by Mignon Cristofoli, Chin-Ping Kung, Jonathan Hadgraft, Majella E. Lane and Bruno C. Sil

Pharmaceutics 2021, 13(6), 909; https://doi.org/10.3390/pharmaceutics13060909 - 20 Jun 2021

Cited by 18 | Viewed by 3813

Abstract

Ion pairing is a strategy used to increase the permeation of topically applied ionised drugs. Formation occurs when the electrostatic energy of attraction between oppositely charged ions exceeds their mean thermal energy, making it possible for them to draw together and attain a [...] Read more.

Ion pairing is a strategy used to increase the permeation of topically applied ionised drugs. Formation occurs when the electrostatic energy of attraction between oppositely charged ions exceeds their mean thermal energy, making it possible for them to draw together and attain a critical distance. These ions then behave as a neutral species, allowing them to partition more readily into a lipid environment. Partition coefficient studies may be used to determine the potential of ions to pair and partition into an organic phase but cannot be relied upon to predict flux. Early researchers indicated that temperature, size of ions and dielectric constant of the solvent system all contributed to the formation of ion pairs. While size is important, this may be outweighed by improved lipophilicity of the counter ion due to increased length of the carbon chain. Organic counter ions are more effective than inorganic moieties in forming ion pairs. In addition to being used to increase permeation, ion pairs have been used to control and even prevent permeation of the active ingredient. They have also been used to stabilise solid lipid nanoparticle formulations. Ion pairs have been used in conjunction with permeation enhancers, and permeation enhancers have been used as counter ions in ion pairing. This review attempts to show the various ways in which ion pairs have been used in drug delivery via the skin. It also endeavours to extract and consolidate common approaches in order to inform future formulations for topical and transdermal delivery. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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19 pages, 655 KiB

Open AccessReview

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

by Tanja Ilić, Ivana Pantelić and Snežana Savić

Pharmaceutics 2021, 13(5), 710; https://doi.org/10.3390/pharmaceutics13050710 - 13 May 2021

Cited by 31 | Viewed by 3839

Abstract

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees [...] Read more.

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches. Full article

(This article belongs to the Special Issue Semisolid Dosage (Volume II))

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