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Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (14 October 2022) | Viewed by 38258

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Special Issue Editor

Prof. Dr. María Ángeles Peña Fernández

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Departamento Ciencias Biomédicas, Facultad de Farmacia, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain
Interests: drug formulation; pharmaceutical technology; formulation development and characterization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The processes of solubilization and controlled release of drugs that are not very soluble in water are of great relevance to the pre-formulation of drugs in pharmaceutical developments.

In recent years, a large number of drugs have been industrialized, but almost 70% of them have low solubility in water, which limits their dissolution rate and, consequently, their bioavailability. Undoubtedly, it is a problem of far-reaching repercussions for the pharmaceutical industry, so the discovery of new technological tools for the hydrosolubilization of drugs that do not affect their physical–chemical and therapeutic properties will constitute an extraordinary achievement.

On the other hand, from a pharmacological point of view, the search for knowledge of the interaction mechanism and the different properties of drug-controlled release systems is currently of great importance in drug formulation, especially in relation to their efficacy therapy, as well as achieving the correct amount of active ingredient, the right time and the precise place of action.

This Special Issue is dedicated to the latest advances in solubilization and controlled release processes for poorly soluble drugs. We invite authors to submit original research or review articles on these topics, including the development of novel solubilization strategies, as well as innovative alternative methods to obtain new controlled-release pharmaceutical forms, suitable for a specific patient and the pathology to be treated, without forgetting the best form of administration to obtain the optimal efficacy and safety of the drugs.

Dr. María Peña Fernández
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

drug formulation
solubilization
controlled release systems
solubility
poor water-soluble drugs

Published Papers (14 papers)

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Editorial

Jump to: Research, Review

3 pages, 199 KiB

Open AccessEditorial

Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs

by M. A. Peña

Pharmaceuticals 2022, 15(11), 1353; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15111353 - 02 Nov 2022

Cited by 1 | Viewed by 1406

Abstract

The processes of solubilization and controlled release of drugs that are poorly soluble in water are highly relevant in drug preformulation studies in pharmaceutical development [...] Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

Research

Jump to: Editorial, Review

27 pages, 12032 KiB

Open AccessArticle

Combination of Dissolving Microneedles with Nanosuspension and Co-Grinding for Transdermal Delivery of Ketoprofen

by Delly Ramadon, Fathin Ulayya, Annisa Sakinah Qur’ani, Iskandarsyah Iskandarsyah, Yahdiana Harahap, Qonita Kurnia Anjani, Vania Aileen, Pietradewi Hartrianti and Ryan F. Donnelly

Pharmaceuticals 2023, 16(3), 378; https://0-doi-org.brum.beds.ac.uk/10.3390/ph16030378 - 01 Mar 2023

Cited by 7 | Viewed by 2621

Abstract

Ketoprofen is an anti-inflammatory agent that may cause gastric irritation if administered orally. Dissolving microneedles (DMN) can be a promising strategy to overcome this issue. However, ketoprofen has a low solubility; therefore, it is essential to enhance its solubility using certain methods, namely nanosuspension (NS) and co-grinding (CG). This research aimed to formulate DMN containing ketoprofen-loaded NS and CG. Ketoprofen NS was formulated with poly(vinyl alcohol) (PVA) at concentrations of 0.5%, 1%, and 2%. CG was prepared by grinding ketoprofen with PVA or poly(vinyl pyrrolidone) (PVP) at different drug–polymer ratios. The manufactured ketoprofen-loaded NS and CG were evaluated in terms of their dissolution profile. The most promising formulation from each system was then formulated into microneedles (MNs). The fabricated MNs were assessed in terms of their physical and chemical properties. An in vitro permeation study using Franz diffusion cells was also carried out. The most promising MN-NS and MN-CG formulations were F4-MN-NS (PVA 5%-PVP 10%), F5-MN-NS (PVA 5%-PVP 15%), F8-MN-CG (PVA 5%-PVP 15%), and F11-MN-CG (PVA 7.5%-PVP 15%), respectively. The cumulative amounts of drug permeated after 24 h for F5-MN-NS and F11-MN-CG were 3.88 ± 0.46 µg and 8.73 ± 1.40 µg, respectively. In conclusion, the combination of DMN with nanosuspension or a co-grinding system may be a promising strategy for delivering ketoprofen transdermally. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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19 pages, 6669 KiB

Open AccessArticle

Surfactant Mediated Accelerated and Discriminatory In Vitro Drug Release Method for PLGA Nanoparticles of Poorly Water-Soluble Drug

by Ritu Gupta, Yuan Chen, Mahua Sarkar and Huan Xie

Pharmaceuticals 2022, 15(12), 1489; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15121489 - 29 Nov 2022

Cited by 3 | Viewed by 2734

Abstract

In vitro drug release testing is an important quality control tool for formulation development. However, the literature has evidence that poly-lactide-co-glycolide (PLGA)-based formulations show a slower in vitro drug release than a real in vivo drug release. Much longer in vitro drug release profiles may not be reflective of real in vivo performances and may significantly affect the timeline for a formulation development. The objective of this study was to develop a surfactant mediated accelerated in vitro drug release method for the PLGA nanoparticles (NPs) of a novel chemotherapeutic agent AC1LPSZG, a model drug with a poor solubility. The Sotax USP apparatus 4 was used to test in vitro drug release in a phosphate buffer with a pH value of 6.8. The sink conditions were improved using surfactants in the order of sodium lauryl sulfate (SLS) < Tween 80 < cetyltrimethylammonium bromide (CTAB). The dissolution efficiency (DE) and area under the dissolution curve (AUC) were increased three-fold when increasing the CTAB concentration in the phosphate buffer (pH 6.8). Similar Weibull release kinetics and good linear correlations (R²~0.99) indicated a good correlation between the real-time in vitro release profile in the phosphate buffer (pH 6.8) and accelerated release profiles in the optimized medium. This newly developed accelerated and discriminatory in vitro test can be used as a quality control tool to identify critical formulation and process parameters to ensure a batch-to-batch uniformity. It may also serve as a surrogate for bioequivalence studies if a predictive in vitro in vivo correlation (IVIVC) is obtained. The results of this study are limited to AC1LPSZG NPs, but a similar consideration can be extended to other PLGA-based NPs of drugs with similar properties and solubility profiles. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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15 pages, 3546 KiB

Open AccessArticle

Constructing an Intelligent Model Based on Support Vector Regression to Simulate the Solubility of Drugs in Polymeric Media

by Sait Senceroglu, Mohamed Arselene Ayari, Tahereh Rezaei, Fardad Faress, Amith Khandakar, Muhammad E. H. Chowdhury and Zanko Hassan Jawhar

Pharmaceuticals 2022, 15(11), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15111405 - 14 Nov 2022

Cited by 2 | Viewed by 1502

Abstract

This study constructs a machine learning method to simultaneously analyze the thermodynamic behavior of many polymer–drug systems. The solubility temperature of Acetaminophen, Celecoxib, Chloramphenicol, D-Mannitol, Felodipine, Ibuprofen, Ibuprofen Sodium, Indomethacin, Itraconazole, Naproxen, Nifedipine, Paracetamol, Sulfadiazine, Sulfadimidine, Sulfamerazine, and Sulfathiazole in 1,3-bis[2-pyrrolidone-1-yl] butane, Polyvinyl Acetate, Polyvinylpyrrolidone (PVP), PVP K12, PVP K15, PVP K17, PVP K25, PVP/VA, PVP/VA 335, PVP/VA 535, PVP/VA 635, PVP/VA 735, Soluplus analyzes from a modeling perspective. The least-squares support vector regression (LS-SVR) designs to approximate the solubility temperature of drugs in polymers from polymer and drug types and drug loading in polymers. The structure of this machine learning model is well-tuned by conducting trial and error on the kernel type (i.e., Gaussian, polynomial, and linear) and methods used for adjusting the LS-SVR coefficients (i.e., leave-one-out and 10-fold cross-validation scenarios). Results of the sensitivity analysis showed that the Gaussian kernel and 10-fold cross-validation is the best candidate for developing an LS-SVR for the given task. The built model yielded results consistent with 278 experimental samples reported in the literature. Indeed, the mean absolute relative deviation percent of 8.35 and 7.25 is achieved in the training and testing stages, respectively. The performance on the largest available dataset confirms its applicability. Such a reliable tool is essential for monitoring polymer–drug systems’ stability and deliverability, especially for poorly soluble drugs in polymers, which can be further validated by adopting it to an actual implementation in the future. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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20 pages, 5861 KiB

Open AccessArticle

Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs

by Fabian-Pascal Schmied, Alexander Bernhardt and Sandra Klein

Pharmaceuticals 2022, 15(9), 1135; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15091135 - 11 Sep 2022

Cited by 9 | Viewed by 3054

Abstract

The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in M_w. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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23 pages, 8645 KiB

Open AccessArticle

Bilosomes as Nanoplatform for Oral Delivery and Modulated In Vivo Antimicrobial Activity of Lycopene

by Reem Binsuwaidan, Amal A. Sultan, Walaa A. Negm, Nashwah G. M. Attallah, Moneerah J. Alqahtani, Ismail A. Hussein, Moataz A. Shaldam, Suzy A. El-Sherbeni and Engy Elekhnawy

Pharmaceuticals 2022, 15(9), 1043; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15091043 - 24 Aug 2022

Cited by 14 | Viewed by 3502

Abstract

Owing to the disseminating resistance among pathogenic bacteria, especially Klebsiella pneumoniae, there is a high need for alternate compounds with antibacterial activity. Herein, lycopene was isolated from Lycopersicon esculentum L. Molecular docking approach was employed to explore lycopene binding affinity to selected vital proteins of K. pneumoniae with the binding mechanisms being investigated. This proposed a promising antibacterial activity of lycopene. However, the pharmacological use of lycopene is hampered by its poor solubility and limited oral bioavailability. Accordingly, bilosomes were fabricated for oral lycopene delivery. The computed entrapment efficiency, mean vesicular size, and zeta potential values for the optimized formulation were 93.2 ± 0.6%, 485.8 ± 35.3 nm, and −38.3 ± 4, respectively. In vitro drug release studies revealed controlled lycopene release from constructed bilosomes, with the drug liberation being based on the Higuchi kinetics model. Transmission electron microscopic evaluation of bilosomes revealed spherical nanovesicles free from aggregates. Moreover, the in vitro and in vivo antibacterial activity of lycopene and its constructed formulations against multidrug-resistant K. pneumoniae isolates were explored. The optimized bilosomes exhibited the lowest minimum inhibitory concentrations ranging from 8 to 32 µg/mL. In addition, scanning electron microscopy revealed remarkable deformation and lysis of the bilosomes-treated bacterial cells. Regarding in vivo investigation, a lung infection model in mice was employed. The tested bilosomes reduced the inflammation and congestion in the treated mice’s lung tissues, resulting in normal-sized bronchioles and alveoli with very few congested vessels. In addition, it resulted in a significant reduction in pulmonary fibrosis. In conclusion, this study investigated the potential activity of the naturally isolated lycopene in controlling infections triggered by multidrug-resistant K. pneumoniae isolates. Furthermore, it introduced bilosomes as a promising biocompatible nanocarrier for modulation of oral lycopene delivery and in vivo antimicrobial activity. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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25 pages, 5954 KiB

Open AccessArticle

Determination of the Dissolution/Permeation and Apparent Solubility for Microencapsulated Emamectin Benzoate Using In Vitro and Ex Vivo Salmo salar Intestine Membranes

by Victoria Molina, Carlos von Plessing, Alex Romero, Sergio Benavides, José Miguel Troncoso, José Ricardo Pérez-Correa and Wendy Franco

Pharmaceuticals 2022, 15(6), 652; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15060652 - 25 May 2022

Cited by 1 | Viewed by 1963

Abstract

In this work, two microencapsulation techniques were used to protect and improve the absorption of emamectin benzoate (EB), which is an antiparasitic drug used to control Caligus rogercresseyi. EB has a low aqueous solubility, which affects its absorption in the intestine of Salmo salar. Microparticles were produced by spray drying and ionic gelation, using Soluplus^® (EB–SOL) and sodium alginate (EB–ALG) as polymers, respectively. Studies were conducted on dissolution/permeation, apparent permeability (Papp), apparent solubility (Sapp), and absorption using synthetic and biological membranes. Based on these results, the amount of EB in the microparticles needed to achieve a therapeutic dose was estimated. The EB–ALG microparticles outperformed both EB–SOL and free EB, for all parameters analyzed. The results show values of 0.45 mg/mL (80.2%) for dissolution/permeation, a Papp of 6.2 mg/mL in RS–L, an absorption of 7.3% in RS, and a Sapp of 53.1% in EM medium. The EB–ALG microparticles decrease the therapeutic dose necessary to control the parasite, with values of 3.0⁻² mg/mL and 1.1⁻² mg/mL for EB in EM and RS, respectively. The Korsmeyer–Peppas kinetic model was the best model to fit the EB–ALG and EB–SOL dissolution/permeation experiments. In addition, some of our experimental results using synthetic membranes are similar to those obtained with biological membranes, which suggests that, for some parameters, it is possible to replace biological membranes with synthetic membranes. The encapsulation of EB by ionic gelation shows it is a promising formulation to increase the absorption of the poorly soluble drug. In contrast, the spray-dried microparticles produced using Soluplus^® result in even less dissolution/permeation than free EB, so the technique cannot be used to improve the solubility of EB. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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17 pages, 2866 KiB

Open AccessArticle

Development of Nanocrystal Compressed Minitablets for Chronotherapeutic Drug Delivery

by Nagaraja Sreeharsha, Nimbagal Raghavendra Naveen, Posina Anitha, Prakash S. Goudanavar, Sundarapandian Ramkanth, Santosh Fattepur, Mallikarjun Telsang, Mohammed Habeebuddin and Md. Khalid Answer

Pharmaceuticals 2022, 15(3), 311; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15030311 - 04 Mar 2022

Cited by 14 | Viewed by 2258

Abstract

The present work aimed to develop a chronotherapeutic system of valsartan (VS) using nanocrystal formulation to improve dissolution. VS nanocrystals (VS-NC) were fabricated using modified anti-solvent precipitation by employing a Box–Behnken design to optimize various process variables. Based on the desirability approach, a formulation containing 2.5% poloxamer, a freezing temperature of −25 °C, and 24 h of freeze-drying time can fulfill the optimized formulation’s requirements to result in a particle size of 219.68 nm, 0.201 polydispersity index, and zeta potential of −38.26 mV. Optimized VS-NC formulation was compressed (VNM) and coated subsequently with ethyl cellulose and HPMC E 5. At the same time, fast dissolving tablets of VS were designed, and the best formulation was loaded with VNM into a capsule size 1 (average fill weight—400–500 mg, lock length—19.30 mm, external diameter: Cap—6.91 mm; Body—6.63 mm). The final tab in cap (tablet-in-capsule) system was studied for in vitro dissolution profile to confirm the chronotherapeutic release of VS. As required, a bi-pulse release of VS was identified with a lag time of 5 h. The accelerated stability studies confirmed no significant changes in the dissolution profiles of the tab in cap system (f₂ similarity profile: >90). To conclude, the tab in cap system was successfully developed to induce a dual pulsatile release, which will ensure bedtime dosing with release after a lag-time to match with early morning circadian spikes. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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13 pages, 3489 KiB

Open AccessArticle

New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

by Xia Niu, Xiaomei Wang, Bingyu Niu, Yucheng Wang, Hongwei He and Guiling Li

Pharmaceuticals 2022, 15(1), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15010085 - 11 Jan 2022

Cited by 5 | Viewed by 1578

Abstract

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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20 pages, 3178 KiB

Open AccessArticle

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

by Szymon Sip, Magdalena Paczkowska-Walendowska, Natalia Rosiak, Andrzej Miklaszewski, Katarzyna Grabańska-Martyńska, Karolina Samarzewska and Judyta Cielecka-Piontek

Pharmaceuticals 2021, 14(8), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080712 - 23 Jul 2021

Cited by 17 | Viewed by 3098

Abstract

Chitosan is a valued excipient due to its biocompatibility properties and increasing solubility of poorly water-soluble drugs. The research presented in this paper concerns the preparation of binary combinations of chitosan (deacetylated chitin) with carvedilol (beta-blocker) to develop a formulation with a modified carvedilol release profile. As part of the research, six physical mixtures of chitosan with carvedilol were obtained and identified by spectral (PXRD, FT-IR, and Raman), thermal (DSC), and microscopic (SEM) methods. The next stage of the research estimated the profile changes and the dissolution rate for carvedilol in the obtained drug delivery systems; the reference sample was pure carvedilol. The studies were conducted at pH = 1.2 and 6.8, simulating the gastrointestinal tract conditions. Quantitative changes of carvedilol were determined using the developed isocratic UHPLC-DAD method. Established apparent permeability coefficients proved the changes in carvedilol’s permeability after introducing a drug delivery system through membranes simulating the gastrointestinal tract and skin walls. A bioadhesive potential of carvedilol–chitosan systems was confirmed using the in vitro model. The conducted research and the obtained results indicate a significant potential of using chitosan as an excipient in modern oral or epidermal drug delivery systems of carvedilol. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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24 pages, 5567 KiB

Open AccessArticle

Optimization of Novel Naproxen-Loaded Chitosan/Carrageenan Nanocarrier-Based Gel for Topical Delivery: Ex Vivo, Histopathological, and In Vivo Evaluation

by Sobia Noreen, Fahad Pervaiz, Akram Ashames, Manal Buabeid, Khairi Fahelelbom, Hina Shoukat, Irsah Maqbool and Ghulam Murtaza

Pharmaceuticals 2021, 14(6), 557; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060557 - 11 Jun 2021

Cited by 19 | Viewed by 4477

Abstract

Naproxen (NAP) is commonly used for pain, inflammation, and stiffness associated with arthritis. However, systemic administration is linked with several gastrointestinal tract (GIT) side effects. The present work aims to prepare and evaluate NAP nanoparticulate shells of chitosan (CS) and carrageenan (CRG) loaded into a Carbopol 940 (Ca-940) gel system with unique features of sustained drug delivery as well as improved permeation through a topical route. Moreover, this study aims to evaluate its ex vivo, histopathological, and in vivo anti-inflammatory activity in albino Wistar rats. The percentage of ex vivo drug permeation patterns in the optimized formulation (No) was higher (88.66%) than the control gel (36.195%). Oral toxicity studies of developed nanoparticles in albino rabbits showed that the NAP-loaded CS/CRG are non-toxic and, upon histopathological evaluation, no sign of incompatibility was observed compared to the control group. A In Vivo study showed that the optimized gel formulation (No) was more effective than the control gel (Nc) in treating arthritis-associated inflammation. The sustained permeation and the absence of skin irritation make this novel NAP nanoparticle-loaded gel based on CS/CRG a suitable drug delivery system for topical application and has the potential for improved patient compliance and reduced GIT-related side effects in arthritis. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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16 pages, 2340 KiB

Open AccessArticle

Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability

by Gabriela Wiergowska, Dominika Ludowicz, Kamil Wdowiak, Andrzej Miklaszewski, Kornelia Lewandowska and Judyta Cielecka-Piontek

Pharmaceuticals 2021, 14(5), 453; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050453 - 11 May 2021

Cited by 6 | Viewed by 2761

Abstract

To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients—hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)—were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques—X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (P_{app crystalline VAR} = 6.83 × 10⁻⁶ cm/s vs. P_{app amorphous VAR} = 8.75 × 10⁻⁶ cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5—more than 1.5-fold increase (P_{app amorphous VAR} = 8.75 × 10⁻⁶ cm/s vs. P_{app amorphous VAR:β-CD 1:5} = 13.43 × 10⁻⁶ cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and β-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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14 pages, 2223 KiB

Open AccessArticle

Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections

by Carlos Benavent, Carlos Torrado-Salmerón and Santiago Torrado-Santiago

Pharmaceuticals 2021, 14(5), 397; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050397 - 22 Apr 2021

Cited by 6 | Viewed by 2642

Abstract

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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Review

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26 pages, 1807 KiB

Open AccessReview

Technologies for Solubility, Dissolution and Permeation Enhancement of Natural Compounds

by Meshal Alshamrani, Muhammad Khalid Khan, Barkat Ali Khan, Ahmad Salawi and Yosif Almoshari

Pharmaceuticals 2022, 15(6), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15060653 - 25 May 2022

Cited by 6 | Viewed by 2794

Abstract

The current review is based on the advancements in the field of natural therapeutic agents which could be utilized for a variety of biomedical applications and against various diseases and ailments. In addition, several obstacles have to be circumvented to achieve the desired therapeutic effectiveness, among which limited dissolution and/or solubility and permeability are included. To counteract these issues, several advancements in the field of natural therapeutic substances needed to be addressed. Therefore, in this review, the possible techniques for the dissolution/solubility and permeability improvements have been addressed which could enhance the dissolution and permeability up to several times. In addition, the conventional and modern isolation and purification techniques have been emphasized to achieve the isolation and purification of single or multiple therapeutic constituents with convenience and smarter approaches. Moreover, a brief overview of advanced natural compounds with multiple therapeutic effectiveness have also been anticipated. In brief, enough advancements have been carried out to achieve safe, effective and economic use of natural medicinal agents with improved stability, handling and storage. Full article

(This article belongs to the Special Issue Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs)

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