Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals—Essential Influence of Excipients

Many active pharmaceutical ingredients (API) possess poor aqueous solubility and thus lead to poor bioavailability upon oral administration and topical application. Nanocrystals have a well-established, universal formulation approach to overcome poor solubility. Various nanocrystal-based products have entered the market for oral application. However, their use in dermal formulations is relatively novel. Previous studies confirmed that nanocrystals are a superior formulation principle to improve the dermal penetration of poorly soluble API. Other studies showed that nanocrystals can also be used to target the hair follicles where they create a drug depot, enabling long acting drug therapy with only one application. Very recent studies show that also the vehicle in which the nanocrystals are incorporated can have a tremendous influence on the pathway of the API and the nanocrystals. In order to elucidate the influence of the excipient in more detail, a systematic study was conducted to investigate the influence of excipients on the penetration efficacy of the formulated API and the pathway of nanocrystals upon dermal application. Results showed that already small quantities of excipients can strongly affect the passive dermal penetration of curcumin and the hair follicle targeting of curcumin nanocrystals. The addition of 2% ethanol promoted hair follicle targeting of nanocrystals and hampered passive diffusion into the stratum corneum of the API, whereas the addition of glycerol hampered hair follicle targeting and promoted passive diffusion. Propylene glycol was found to promote both pathways. In fact, the study proved that formulating nanocrystals to improve the bioefficacy of poorly soluble API upon dermal application is highly effective. However, this is only true, if the correct excipient is selected for the formulation of the vehicle. The study also showed that excipients can be used to allow for a targeted dermal drug delivery, which enables to control if API should be delivered via passive diffusion and/or as drug reservoir by depositing API in the hair follicles.

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Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Molecules ◽

10.3390/molecules26061633 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1633

Author(s):

Ralph W. Eckert ◽

Sabrina Wiemann ◽

Cornelia M. Keck

Keyword(s):

Drug Delivery ◽

Transdermal Delivery ◽

Aqueous Solubility ◽

Local Concentration ◽

Active Compounds ◽

Drug Products ◽

Dermal Penetration ◽

Penetration Mechanism ◽

Poorly Soluble ◽

Transdermal Penetration

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.

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Nano-Lipidic Carriers as a Tool for Drug Targeting to the Pilosebaceous Units

Current Pharmaceutical Design ◽

10.2174/1381612826666200515133142 ◽

2020 ◽

Vol 26 (27) ◽

pp. 3251-3268

Author(s):

Shweta Ramkar ◽

Abhishek K. Sah ◽

Nagendra Bhuwane ◽

Ishwari Choudhary ◽

Narayan Hemnani ◽

...

Keyword(s):

Drug Delivery ◽

Hair Follicle ◽

Hair Follicles ◽

Prolonged Release ◽

Pilosebaceous Unit ◽

Tissue Targeting ◽

Bulge Region ◽

Drug Reservoir ◽

Fast Transport ◽

Topical Applications

The pilosebaceous unit is the triad comprising of hair follicle, arrector pilli muscle, and sebaceous gland. Drug delivery to and through the hair follicles has garnered much attention of the researchers and the hair follicles represent an attractive target site via topical applications. They are bordered by capillaries and antigenpresenting cells, connected to the sebaceous glands and the bulge region of the hair follicle anchors the stem cells. The nano lipid carriers have the propensity to penetrate through the skin via transcellular route, intracellular route and follicular route. It has been established that nano lipid carriers have the potential for follicular drug delivery and provide some advantages over conventional pathways, including improved bioavailability, enhanced penetration depth, fast transport into the skin, tissue targeting and form a drug reservoir for prolonged release. This review describes the pilosebaceous unit (PSU) and related diseases and the recent lipid-based nanotechnology approaches for drug delivery to the follicular unit as well as related issues. Different types of nano lipid carriers, including ethosomes, liposomes, nanoparticles, solid lipid nanoparticles (SLNs), and nano lipid carriers (NLCs) have been reported for follicular drug delivery. Targeted drug delivery with nano-lipid carriers has the potential to augment the efficacy of drugs/bioactives to treat diseases of PSU. This review systematically introduces the activities of different formulations and the use of nano lipid carriers in treating PSU related disorders like alopecia, acne, and hirsutism.

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Self-microemulsion Technology for Water-insoluble Drug Delivery

Current Nanoscience ◽

10.2174/1573413715666190112122107 ◽

2019 ◽

Vol 15 (6) ◽

pp. 576-588 ◽

Cited By ~ 1

Author(s):

Beibei Yan ◽

Yu Gu ◽

Juan Zhao ◽

Yangyang Liu ◽

Lulu Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Aqueous Solubility ◽

Delivery Systems ◽

Poorly Soluble Drugs ◽

New Chemical Entities ◽

Poorly Soluble ◽

Water Insoluble Drug ◽

Semi Solid ◽

Solidification Technology

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

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Self Emulsifying Drug Delivery System: A Recent Approach

Asian Journal of Chemistry ◽

10.14233/ajchem.2019.21569 ◽

2019 ◽

Vol 31 (4) ◽

pp. 751-759 ◽

Cited By ~ 1

Author(s):

Sabitri Bindhani ◽

S. Mohapatra ◽

R.K. Kar

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Oral Absorption ◽

Scale Up ◽

Aqueous Solubility ◽

Oral Drug ◽

Recent Approach ◽

Poorly Soluble

In recent years, nearly 40 % newer drugs compounds are hydrophobic in nature, which is a major challenge now-a-days for oral drug delivering due to low aqueous solubility. Lipid based drug delivery system is one of the favourable approach for poorly soluble compounds which can improve the drug absorption and oral bioavailability. Due to ion-pairing with appropriate surfactant and co-surfactant the macromolecular drug molecular oil droplet being found in the gut flow oral absorption which sufficiently stable towards lipase. Due to the formation of emulsified drug in micron level, it can efficiently endow the oral bioavailability. Several comprehensive papers have been published in the literature illustration diverse type of lipid based formulation with recent advancements. This article is based on an exhaustive and updated review on newer technology which out line an explicit discussion on its formulations and industrial scale up.

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Are lipid nanoparticles really superior? A holistic proof of concept study

Drug Delivery and Translational Research ◽

10.1007/s13346-021-01021-5 ◽

2021 ◽

Author(s):

Sabrina Wiemann ◽

Cornelia M. Keck

Keyword(s):

Chemical Stability ◽

Chemical Properties ◽

Lipid Nanoparticles ◽

Proof Of Concept ◽

Beneficial Effects ◽

Dermal Penetration ◽

Physico Chemical ◽

Nanoparticle Formulation ◽

Dermal Drug Delivery ◽

Dermal Application

AbstractLipid nanoparticles are a successful carrier system for dermal drug delivery. They possess various beneficial properties, i.e., increased chemical stability for chemically labile compounds, increased dermal penetration of active compounds, or skin carrying properties after dermal application due to the formation of a so-called “invisible patch.” Despite manifold studies showing these properties individually, a study that investigates if one lipid nanoparticle formulation can really combine all the above-mentioned benefits at once is not yet available. In the present study, lipid nanoparticles (NLC) were produced and characterized regarding their physico-chemical properties. The chemical stability of the incorporated active ingredient (AI) was determined, as well as the dermal penetration efficacy of the AI, and the skin carrying properties of the NLC after dermal penetration. The properties of the NLC were compared to classical formulations, i.e., AI dissolved in pure oil, an o/w cream base and a nanoemulsion. All formulations contained similar lipids and emulsifiers, which allowed for a direct comparison of the different properties. NLC were shown to provide most efficient chemical stabilization and most efficient dermal penetration for the AI. The formation of the invisible patch was shown for the NLC but not for the other formulations. Skin hydration and skin carrying properties were also most pronounced for the NLC. Results provide evidence that NLC can combine all beneficial effects that were previously described in one formulation. Thus, providing evidence that NLC are a holistically superior formulation principle when compared to other formulation principles. Graphical abstract

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Recent Advances in Self-Emulsifying Drug Delivery Systems

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.1.1 ◽

2015 ◽

Vol 8 (1) ◽

pp. 2693-2697

Author(s):

Amol S Deshmukh

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Aqueous Solubility ◽

Oral Route ◽

Delivery Systems ◽

Novel Technologies ◽

Oral Formulations ◽

Modern Drug ◽

New Chemical Entities ◽

Poorly Soluble

Oral route has always been preferred route for formulators and has dominated over other routes of administrations. But major problem encountered in oral formulations (as estimated more than 50 % of oral formulations are found to be poorly aqueous soluble), is low bioavailability, giving rise to further problems like, high inter and intra subject variability, lack of dose uniformity and finally leading to therapeutic failure. Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. Particularly for BCS class II substances, the bioavailability may be enhanced by increasing the solubility and dissolution rate of the drug in the gastro-intestinal fluids. The newer and novel technologies developed in recent year for troubleshooting such above problems. This review describes an overview of SEDDS as a capable approach to effectively capture the problem of poorly soluble molecules and give the novel approaches for evaluation of the SEDDS. Self-emulsifying drug delivery systems (SEDDS) are isotropic mixtures of drug, lipids and surfactants, usually with one or more hydrophilic co-solvents or co-emulsifiers.

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Self-Emulsifying Formulations: A Pharmaceutical Review

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i3.3981 ◽

2020 ◽

Vol 10 (3) ◽

pp. 231-240

Author(s):

Chukwuma Agubata

Keyword(s):

Drug Delivery ◽

Oral Delivery ◽

Drug Delivery Systems ◽

Aqueous Solubility ◽

Oral Route ◽

Concept Design ◽

Lipophilic Drugs ◽

Oil In Water ◽

Poorly Soluble ◽

Mild Agitation

The oral route of drug delivery is commonly utilized for administration of medicines and is particularly preferred for the treatment of many chronic diseases which require continuous ingestion over a reasonably prolonged period of time. However the oral delivery of lipophilic drugs presents a major obstacle because of their low aqueous solubility. The aqueous solubility of a drug is a crucial determinant of its dissolution rate, absorption and bioavailability. Drugs with relatively high intrinsic lipophilicity can be dissolved in appropriate mixtures of oils/lipids, surfactants, cosolvents which can rapidly form oil-in-water (o/w) fine emulsions when dispersed in aqueous phase under mild agitation or mixing. These isotropic self-emulsifying formulations or self-emulsifying drug delivery systems are effective for delivery of poorly soluble, lipophilic drugs by dispersing the drugs within fine oil droplets in emulsions and this solubilization of drugs can then improve its absorption, bioavailability and therapeutic efficacy. The present paper reviews the concept, design, formulation, characterization and applications of self-emulsifying formulations. Keywords: Self-Emulsifying Formulations, lipophilicity, emulsions

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Nanoliposome-loaded antifungal drugs for dermal administration: A review

Current Medical Mycology ◽

10.18502/cmm.7.1.6247 ◽

2021 ◽

Author(s):

Peyman Asadi ◽

Ahmad Mehravaran ◽

Nahid Soltanloo ◽

Mahdi Abastabar ◽

Javad Akhtari

Keyword(s):

Drug Delivery ◽

Stratum Corneum ◽

Fungal Infections ◽

Skin Penetration ◽

Antifungal Drugs ◽

Terbinafine Hydrochloride ◽

Dermal Administration ◽

Almost All ◽

Dermal Drug Delivery ◽

Dermal Application

Cutaneous fungal infections are the fourth most common health problem, which involves approximately billion people worldwide. Drug delivery to the skin seems to be the best choice for superficial fungal infections. Topical formulations can release a sufficient amount of drug in therapeutical concentrations and permeate higher layers of the skin like the stratum corneum. As the outermost layer of the epidermis, the stratum corneum prevents the drug from penetrating the skin. Liposomes, especially nanosized as topical drug delivery systems to the skin, can show various functions depending on their size, lipids and cholesterol components, the percent of ingredients, lamellarity, and surface charge. Nanoliposomes can increase permeation through the stratum corneum, decrease systemic effects with their localizing actions, and overcome many dermal drug delivery obstacles. Antifungal drugs, such as croconazole, econazole, fluconazole, ketoconazole, terbinafine hydrochloride, tolnaftate, and miconazole entrapped in liposomes have indicated improved skin penetration and localizing effects. According to the literature review summarized in this paper, many studies have identified liposomes as a powerful carrier for topical antifungal drug delivery to the skin. However, a few studies introduced new generations of liposomes like ethosomes and transfersomes. This paper was conducted on almost all liposomal studies of antifungal drugs with dermal application.

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Solubility Enhancement of Poorly Soluble Drug Simvastatin by Solid Dispersion Technique

Research in Pharmacy and Health Sciences ◽

10.32463/rphs.2016.v02i02.16 ◽

2016 ◽

Vol 2 (2) ◽

pp. 91-95

Author(s):

Neelima Rani T ◽

Pavani A ◽

Sobhita Rani P ◽

Srilakshmi N

Keyword(s):

Dissolution Rate ◽

Drug Carrier ◽

Solid Dispersions ◽

Aqueous Solubility ◽

Onset Of Action ◽

Kneading Method ◽

Wetting Property ◽

Poorly Soluble ◽

Dispersion Technique ◽

Low Solubility

This study aims to formulate solid dispersions (SDs) of Simvastatin (SIM) to improve the aqueous solubility, dissolution rate and to facilitate faster onset of action. Simvastatin is a BCS class II drug having low solubility & therefore low oral bioavailability. In the present study, SDs of simvastatin different drug-carrier ratios were prepared by kneading method. The results showed that simvastatin solubility & dissolution rate enhanced with polymer SSG in the ratio 1:7 due to increase in wetting property or possibly may be due to change in crystallinity of the drug.

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