Encapsulation and drug release of poorly water soluble nifedipine from bio-carriers

Purposes: Aims of this study are dissolution enhancement of a poorly water-soluble drug by nano-sized solid dispersion and investigation of machenism of drug release from the solid dispersion. A drug for osteoporosis treatment was used as the model drug in the study. Methods: melting method was used to prepare the solid dispersion. Drug dissolution rate was investigated at pH 1.2 and pH 6.8. Drug crystallinity was studied using differential scanning calorimetric and powder X-ray diffraction. In addition, droplet size and contact angle of drug were determined to elucidate mechanism of drug release. Results: Drug dissolution from the solid dispersion was significantly increased at pH 1.2 and pH 6.8 as compared to pure drug. Drug crystallinity was changed to partially amorphous. Also dissolution enhancement of drug was due to the improved wettability. The droplet size of drug was in the scale of nano-size when solid dispersion was dispersed in dissolution media. Conclusions: nano-sized solid dispersion in this research was a successful preparation to enhance bioavailability of a poorly water-soluble drug by mechanisms of crystal changes, particle size reduction and increase of wet property.

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Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes

Molecules ◽

10.3390/molecules26092591 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2591

Author(s):

Thuan Thi Duong ◽

Antti Isomäki ◽

Urve Paaver ◽

Ivo Laidmäe ◽

Arvo Tõnisoo ◽

...

Keyword(s):

Thin Film ◽

Drug Release ◽

Size Distribution ◽

Water Soluble ◽

Release Behavior ◽

Uniform Size ◽

Ethanol Injection ◽

Drug Release Behavior ◽

Poorly Water Soluble

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

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A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

Pharmaceutics ◽

10.3390/pharmaceutics13122107 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2107

Author(s):

Bryce W. Barber ◽

Camille Dumont ◽

Philippe Caisse ◽

George P. Simon ◽

Ben J. Boyd

Keyword(s):

Drug Release ◽

Volume Ratio ◽

Water Soluble ◽

Dissolution Time ◽

Lipophilic Drugs ◽

Solid Lipid ◽

Area Of Interest ◽

3D Printed ◽

Poorly Water Soluble ◽

Lipid Formulations

3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.

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Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

Pharmaceuticals ◽

10.3390/ph14121255 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1255

Author(s):

Ju-Hyun Lee ◽

Chulhun Park ◽

Kwon-Yeon Weon ◽

Chin-Yang Kang ◽

Beom-Jin Lee ◽

...

Keyword(s):

Drug Release ◽

Amorphous State ◽

Water Soluble ◽

Pharmacokinetic Data ◽

In Vivo Test ◽

Water Soluble Drug ◽

Absorption Area ◽

Poorly Water Soluble

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

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It is Possible to Achieve Tablets with Good Tabletability from Solid Dispersions – the Case of the High Dose Drug Gemfibrozil

Current Drug Delivery ◽

10.2174/1567201817666201023121948 ◽

2020 ◽

Vol 17 ◽

Author(s):

Eduarda Rocha Bigogno ◽

Luciano Soares ◽

Matheus Henrique Ruela Mews ◽

Melissa Zétola ◽

Giovana Carolina Bazzo ◽

...

Keyword(s):

Drug Release ◽

Dissolution Rate ◽

Solid Dispersions ◽

Water Soluble ◽

Drug Dissolution ◽

Dissolution Enhancement ◽

Poorly Water Soluble Drugs ◽

Water Soluble Drugs ◽

Croscarmellose Sodium ◽

Poorly Water Soluble

Background: Solid dispersions (SDs) have been extensively used to increase dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets. Objective: This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed. Method: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as carrier, according to a 23 factorial design. The formulation variables were: gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed. Results: SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil-HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time. Conclusion: SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug.

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Melt extrusion process for adjusting drug release of poorly water soluble drug felodipine using different polymer matrices

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2018.01.004 ◽

2018 ◽

Vol 114 ◽

pp. 332-345 ◽

Cited By ~ 9

Author(s):

Eirini Palazi ◽

Evangelos Karavas ◽

Panagiotis Barmpalexis ◽

Margaritis Kostoglou ◽

Stavroula Nanaki ◽

...

Keyword(s):

Drug Release ◽

Extrusion Process ◽

Water Soluble ◽

Polymer Matrices ◽

Melt Extrusion ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

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EFFECT OF CROSSLINKER AMOUNT ON HYBRID HYDROGELS SWELLING AND DRUG RELEASE

10.46793/iccbi21.125m ◽

2021 ◽

Author(s):

Maja Markovic ◽

◽

Vesna Panic ◽

Julijana Tadic ◽

Rada Pjanovic

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Targeted Drug Delivery ◽

Targeted Delivery ◽

Water Soluble ◽

Soluble Model ◽

Hybrid Hydrogels ◽

Poorly Water Soluble ◽

Targeted Drug ◽

Model Drug

Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly water- soluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances.

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DESIGN AND DEVELOPMENT OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS (SMEDDS) OF TELMISARTAN FOR ENHANCEMENT OF IN VITRO DISSOLUTION AND ORAL BIOAVAILABILITY IN RABBIT

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i4.27048 ◽

2018 ◽

Vol 10 (4) ◽

pp. 117 ◽

Cited By ~ 1

Author(s):

Suvendu Kumar Sahoo ◽

Padilam Suresh ◽

Usharani Acharya

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Zeta Potential ◽

Droplet Size ◽

Oral Bioavailability ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Water Soluble ◽

Poorly Water Soluble

Objective: The main purpose of this investigation was to prepare self-microemulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of a poorly water soluble drug telmisartan (TLS), a BCS class II drug by improving its dissolution rate. Methods: Self-Emulsifying Drug Delivery Systems (SEDDS) of TLS were formulated using cinnamon essential oil as the oil phase, Gelucire 44/14 as the surfactant and Transcutol HP as co-surfactant. Drug-excipient interactions were studied by FTIR spectroscopy. The formulations were evaluated for its self-emulsifying ability, clarity, and stability of the aqueous dispersion after 48 h and the phase diagram was constructed to optimize the system. Selected formulations were characterized in terms of droplet size distribution, zeta potential, cloud point and were subjected to in vitro drug release studies. The bioavailability of optimized formulation was assessed in New Zealand white rabbits.Results: By considering smaller droplet size, higher zeta potential and faster rate of drug release the formulation TF9 was chosen as optimized SMEDDS formulations. TF9 was robust to different pH media and dilution volumes, remained stable after three cooling-heating cycles and after stored at 4 °C and 25 °C for 3 mo without showing a significant change in droplet size. The pharmacokinetic study in rabbits showed SMEDDS have significantly increased the Cmax and area under the curve (AUC) of TLS compared to suspension (P<0.05).Conclusion: SMEDDS can be an effective oral dosage form for enhancing aqueous solubility and improving oral bioavailability of poorly water soluble drugs.

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COMPARISON AND CHARACTERIZATION OF INCLUSION COMPLEXES AND SOLID DISPERSIONS IN ENHANCEMENT OF DISSOLUTION RATE OF POORLY WATER SOLUBLE DRUG

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.25054 ◽

2018 ◽

Vol 10 (5) ◽

pp. 173

Author(s):

Radha Rani Earle ◽

Rambabu Jammu ◽

Lakshmi Usha ◽

Ratna Kanth Lingam

Keyword(s):

Drug Release ◽

Dissolution Rate ◽

Inclusion Complexes ◽

Solid Dispersions ◽

Water Soluble ◽

Peg 6000 ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

Objective: The purpose of the present study was to enhance solubility and dissolution characteristics of indomethacin by preparing inclusion complexes with hydroxypropyl β-cyclodextrin (HP β-CD) and solid dispersions with PEG 6000 to enhance its in vitro drug release and to further formulate it as a tabletMethods: Solid dispersions (SDs) and inclusion complexes (ICs) of Indomethacin with PEG 6000 and HP β-CD respectively were prepared to enhance the dissolution rate of this poorly water-soluble drug belonging to BCS class II. A comparison was made between two systems: solid dispersions with PEG 6000 obtained using melting and solvent evaporation technique, inclusion complexes with HP β-CD prepared by kneading technique. SDs were prepared in 1:1, 1:2, 1:3 and ICs in 1:0.25, 1:0.5, 1:1 w/w ratios of drug: polymer. Both the systems were characterized by FTIR, SEM, DSC, X-RD.Results: The dissolution of indomethacin increased with the increase in the concentration of the polymers. F4 and F9 formulations showed complete drug release in less than 30 min. Dissolution studies indicated that cyclodextrin complexes showed a better enhancement of dissolution rate when compared to solid dispersions. CDs were found to be more effective than PEGs at lower concentrations. These formulations were further compressed as tablets.Conclusion: The FTIR and DSC studies showed that no interactions existed between the drug and the polymer.

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