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Investigation on the effect of polymer and starch on the tablet properties of lyophilized orally disintegrating tablet

Liew KB, Peh KK

Arch Pharm Res, 2021 Aug;44(8):1-10.
PMID: 25579848 DOI: 10.1007/s12272-014-0542-y

Orally disintegrating tablet (ODT) is a user friendly and convenient dosage form. The study aimed to investigate the effect of polymers and wheat starch on the tablet properties of lyophilized ODT, with dapoxetine as model drug. Three polymers (hydroxypropylmethyl cellulose, carbopol 934P and Eudragit® EPO) and wheat starch were used as matrix forming materials in preparation of lyophilized ODT. The polymeric dispersion was casted into a mould and kept in a freezer at -20 °C for 4 h before freeze dried for 12 h. It was found that increasing in HPMC and Carbopol 934P concentrations produced tablets with higher hardness and longer disintegration time. In contrast, Eudragit® EPO was unable to form tablet with sufficient hardness at various concentrations. Moreover, HPMC seems to have a stronger effect on tablet hardness compared to Carbopol 934P at the same concentration level. ODT of less friable was obtained. Wheat starch acted as binder which strengthen the hardness of ODTs and prolonged the disintegration time. ODT comprising of HPMC and wheat starch at ratio of 2:1 was found to be optimum based upon the tablet properties. The optimum formulation was palatable and 80 % of the drug was released within 30 min in the dissolution study.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Fulltext A Review on Antistaphylococcal Secondary Metabolites from Basidiomycetes

Vallavan V, Krishnasamy G, Zin NM, Abdul Latif M

Molecules, 2020 Dec 11;25(24).
PMID: 33322256 DOI: 10.3390/molecules25245848

Fungi are a rich source of secondary metabolites with several pharmacological activities such as antifungal, antioxidant, antibacterial and anticancer to name a few. Due to the large number of diverse structured chemical compounds they produce, fungi from the phyla Ascomycota, Basidiomycota and Muccoromycota have been intensively studied for isolation of bioactive compounds. Basidiomycetes-derived secondary metabolites are known as a promising source of antibacterial compounds with activity against Gram-positive bacteria. The continued emergence of antimicrobial resistance (AMR) poses a major challenge to patient health as it leads to higher morbidity and mortality, higher hospital-stay duration and substantial economic burden in global healthcare sector. One of the key culprits for AMR crisis is Staphylococcus aureus causing community-acquired infections as the pathogen develops resistance towards multiple antibiotics. The recent emergence of community strains of S. aureus harbouring methicillin-resistant (MRSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) genes associated with increased virulence is challenging. Despite the few significant developments in antibiotic research, successful MRSA therapeutic options are still needed to reduce the use of scanty and expensive second-line treatments. This paper provides an overview of findings from various studies on antibacterial secondary metabolites from basidiomycetes, with a special focus on antistaphylococcal activity.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Fulltext Quality of benzathine penicillin G: A multinational cross-sectional study

Hand RM, Senarathna SMDKG, Page-Sharp M, Gray K, Sika-Paotonu D, Sheel M, et al.

Pharmacol Res Perspect, 2020 12;8(6):e00668.
PMID: 33090729 DOI: 10.1002/prp2.668

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Comparison of Disintegrant-addition Methods on the Compounding of Orodispersible Tablets

Mahesparan VA, Bin Abd Razak FS, Ming LC, Uddin AH, Sarker MZI, Bin LK

Int J Pharm Compd, 2020 3 21;24(2):148-155.
PMID: 32196477

Orodispersible tablets disintegrate rapidly (within 3 minutes) in the oral cavity and release the medicament before swallowing. The mode of disintegrant addition might affect the properties of orodispersible tablets. The objective of this study was to formulate and evaluate orodispersible tablets by studying different modes of disintegration addition with varying concentrations of disintegrants. The wet granulation method was used to produce the orodispersible tablets. Two methods of disintegration addition were compared (i.e., intragranular, extragranular). Three disintegrants (i.e., cornstarch, sodium starch glycolate, crospovidone) were used at three levels (5%, 10%, and 15%) in the study. The formulations were tested for the powder flowability (angle of repose) and characterized physically (hardness, weight, thickness, friability, disintegration time). The mangosteen pericarp extract was used as a model active pharmaceutical ingredient to be incorporated into the optimum formulation. It was observed that the extragranular method produced granules with better flowability compared to that of the intragranular method. Crospovidone was found as the most efficient disintegrant among the three. The optimum formulation selected was one with the highest concentration of crospovidone (15%), which showed the fastest disintegration time. The mode of disintegrant addition into the orodispersible tablets formulation was found to show a marked difference in the disintegration, as well as other physical characteristics of the orodispersible tablets where the extragranular mode of addition showed better property, which caused the orodispersible tablets to disintegrate the fastest.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Effect of processing methods on xylitol-starch base co-processed adjuvant for orally disintegrating tablet application

Bin LK, Helaluddin ABM, Islam Sarker MZ, Mandal UK, Gaurav A

Pak J Pharm Sci, 2020 Mar;33(2):551-559.
PMID: 32276897

Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Exploring the potential of tianeptine matrix tablets: Synthesis, physico-chemical characterization and acute toxicity studies

Salam NA, Naeem MA, Malik NS, Riaz M, Shahiq-Uz-Zaman -, Masood-Ur-Rehman -, et al.

Pak J Pharm Sci, 2020 Jan;33(1(Supplementary)):269-279.
PMID: 32122858

The main objective of the present study was to explore the potential of matrix tablets as extended release dosage form of tianeptine, using HMPC K100 as a polymer. HPMC K100 extended the release of the drug from formulation due to the gel-like structure. Direct compression method was adopted to compress the tablets using different concentrations of polymer. Tablets were evaluated for pre-compression and post-compression parameters. Drug release study showed that tablet extends the release of drug with the increasing concentration of polymer. Drug, polymers and tablets were analyzed and/or characterized for compatibility, degradation, thermal stability, amorphous or crystalline nature via FTIR, DSC, TGA, XRD studies. SEM study predicted that tablets had a uniform structure. HPMC K100 based tablets were similar to that of the reference product. Acute toxicity study conducted on Swiss albino mice showed that matrix tablets were safe and non-toxic, as no changes in physical activity and functions of organs were observed. Biochemical and histopathological study revealed lack of any kind of abnormality in liver and renal function. Moreover, necrotic changes were absent at organ level.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Fulltext Optimization of Processing Parameters of Nanoemulsion Containing Aripiprazole Using Response Surface Methodology

Samiun WS, Ashari SE, Salim N, Ahmad S

Int J Nanomedicine, 2020;15:1585-1594.
PMID: 32210553 DOI: 10.2147/IJN.S198914

BACKGROUND: Aripiprazole, which is a quinolinone derivative, has been widely used to treat schizophrenia, major depressive disorder, and bipolar disorder.
PURPOSE: A Central Composite Rotatable Design (CCRD) of Response Surface Methodology (RSM) was used purposely to optimize process parameters conditions for formulating nanoemulsion containing aripiprazole using high emulsification methods.
METHODS: This design is used to investigate the influences of four independent variables (overhead stirring time (A), shear rate (B), shear time (C), and the cycle of high-pressure homogenizer (D)) on the response variable namely, a droplet size (Y) of nanoemulsion containing aripiprazole.
RESULTS: The optimum conditions suggested by the predicted model were: 120 min of overhead stirring time, 15 min of high shear homogenizer time, 4400 rpm of high shear homogenizer rate and 11 cycles of high-pressure homogenizer, giving a desirable droplet size of nanoemulsion containing aripiprazole of 64.52 nm for experimental value and 62.59 nm for predicted value. The analysis of variance (ANOVA) showed the quadratic polynomial fitted the experimental values with F-value (9.53), a low p-value (0.0003) and a non-significant lack of-fit. It proved that the models were adequate to predict the relevance response. The optimized formulation with a viscosity value of 3.72 mPa.s and pH value of 7.4 showed good osmolality value (297 mOsm/kg) and remained stable for three months in three different temperatures (4°C, 25°C, and 45°C).
CONCLUSION: This proven that response surface methodology is an efficient tool to produce desirable droplet size of nanoemulsion containing aripiprazole for parenteral delivery application.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Emerging frontiers of deep eutectic solvents in drug discovery and drug delivery systems

Zainal-Abidin MH, Hayyan M, Ngoh GC, Wong WF, Looi CY

J Control Release, 2019 12 28;316:168-195.
PMID: 31669211 DOI: 10.1016/j.jconrel.2019.09.019

The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Molecular Dynamics and Physical Stability of Pharmaceutical Co-amorphous Systems: Correlation Between Structural Relaxation Times Measured by Kohlrausch-Williams-Watts With the Width of the Glass Transition Temperature (ΔTg) and the Onset of Crystallization

Chieng N, Teo X, Cheah MH, Choo ML, Chung J, Hew TK, et al.

J Pharm Sci, 2019 12;108(12):3848-3858.
PMID: 31542436 DOI: 10.1016/j.xphs.2019.09.013

The study aims to characterize the structural relaxation times of quench-cooled co-amorphous systems using Kohlrausch-Williams-Watts (KWW) and to correlate the relaxation data with the onset of crystallization. Comparison was also made between the relaxation times obtained by KWW and the width of glass transition temperature (ΔTg) methods (simple and quick). Differential scanning calorimetry, Fourier-transformed infrared spectroscopy, and polarized light microscopy were used to characterize the systems. Results showed that co-amorphous systems yielded a single Tg and ΔCp, suggesting the binary mixtures exist as a single amorphous phase. A narrow step change at Tg indicates the systems were fragile glasses. In co-amorphous nap-indo and para-indo, experimental Tgs were in good agreement with the predicted Tg. However, the Tg of co-amorphous nap-cim and indo-cim were 20°C higher than the predicted Tg, possibly due to stronger molecular interactions. Structural relaxation times below the experimental Tg were successfully characterized using the KWW and ΔTg methods. The comparison plot showed that KWW data are directly proportional to the ½ power of ΔTg data, after adjusting for a small offset. A moderate positive correlation was observed between the onset of crystallization and the KWW data. Structural relaxation times may be useful predictor of physical stability of co-amorphous systems.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

Singh I, Nair RS, Gan S, Cheong V, Morris A

Pharm Dev Technol, 2019 Apr;24(4):448-454.
PMID: 30084268 DOI: 10.1080/10837450.2018.1509347

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis

Fernando HV, Chan LL, Dang N, Santhanes D, Banneheke H, Nalliah S, et al.

Pharm Dev Technol, 2019 Mar;24(3):348-356.
PMID: 29799300 DOI: 10.1080/10837450.2018.1481430

Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid 'burst release' of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the 'non-formulated' drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Conventional versus microwave assisted synthesis, molecular docking and enzyme inhibitory activities of new 3,4,5-trisubstituted-1,2,4-triazole analogues

Virk NA, Rehman A, Abbasi MA, Siddiqui SZ, Rashid U, Iqbal J, et al.

Pak J Pharm Sci, 2018 Jul;31(4(Supplementary)):1501-1510.
PMID: 30058542

N-(Substituted)-5-(1-(4-methoxyphenylsulfonyl)piperidin-4-yl)-4H-1,2,4-triazol-3-ylthio) acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under the impact of various reaction conditions to control the reaction time and the yield of product. Starting from 4-methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4 by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds (8a-k). These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase (bCA-II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 ± 0.38 μM, 11.87±0.19 μM and 26.01±0.55 μM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Effect of storage temperature on the stability of spray dried bacteriophage powders

Leung SSY, Parumasivam T, Nguyen A, Gengenbach T, Carter EA, Carrigy NB, et al.

Eur J Pharm Biopharm, 2018 Jun;127:213-222.
PMID: 29486303 DOI: 10.1016/j.ejpb.2018.02.033

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106-107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Current regulatory requirements and practical approaches for stability analysis of pharmaceutical products: A comprehensive review

Sengupta P, Chatterjee B, Tekade RK

Int J Pharm, 2018 May 30;543(1-2):328-344.
PMID: 29635054 DOI: 10.1016/j.ijpharm.2018.04.007

Different regulatory guidelines recommend establishing stability profile of pharmaceuticals at the time of drug development. The expiry date, retesting period and storage conditions of active drugs or products are established through stability analysis. Several regulatory guidelines exist for stability testing of pharmaceuticals. Mostly, ICH stability guidelines are followed in practice. This guideline recommends to validate stability indicating method using forced degradation samples that contains all possible degradation impurities. ICH guidelines provide general recommendations for inclusion of stability indicating parameters in a stability testing protocol. However, those guidelines do not provide specific requirements and experimental methodology to be followed for stability studies. Due to this gap, often confusion arises in the scientific community in designing stability testing protocol. Therefore, significant variations are observed in reported literature in selection of stability indicating parameters. Procedural dissimilarity amongst reported stability studies is also evident. This review discusses the regulatory guidelines and procedures to follow in performing stability testing of pharmaceuticals. Scope of this review also includes recommendations on practical approaches for designing stability testing protocol to fulfill current regulatory requirements for drug substances and their formulations.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with marked in vivo antitumor activity

Choudhury H, Gorain B, Tekade RK, Pandey M, Karmakar S, Pal TK

Regul Toxicol Pharmacol, 2017 Dec;91:179-189.
PMID: 29080846 DOI: 10.1016/j.yrtph.2017.10.023

Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar systems

Khurana RK, Beg S, Burrow AJ, Vashishta RK, Katare OP, Kaur S, et al.

Eur J Pharm Biopharm, 2017 Dec;121:42-60.
PMID: 28887099 DOI: 10.1016/j.ejpb.2017.09.001

The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul <5min, Dnm <100nm, Rel15min >85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

Shah K, Chan LW, Wong TW

Drug Deliv, 2017 Nov;24(1):1631-1647.
PMID: 29063794 DOI: 10.1080/10717544.2017.1384298

The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Tumor regression and modulation of gene expression via tumor-targeted tocotrienol niosomes

Tan DM, Fu JY, Wong FS, Er HM, Chen YS, Nesaretnam K

Nanomedicine (Lond), 2017 Oct;12(20):2487-2502.
PMID: 28972460 DOI: 10.2217/nnm-2017-0182

AIM: To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols (T3) in breast cancer.
MATERIALS & METHODS: Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy.
RESULTS: When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC50 value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis.
CONCLUSION: Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Fulltext New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study

Taher AT, Origa R, Perrotta S, Kourakli A, Ruffo GB, Kattamis A, et al.

Am J Hematol, 2017 May;92(5):420-428.
PMID: 28142202 DOI: 10.1002/ajh.24668

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Fulltext Aceclofenac nanocrystals with enhanced in vitro, in vivo performance: formulation optimization, characterization, analgesic and acute toxicity studies

Rahim H, Sadiq A, Khan S, Khan MA, Shah SMH, Hussain Z, et al.

Drug Des Devel Ther, 2017;11:2443-2452.
PMID: 28860715 DOI: 10.2147/DDDT.S140626

This study was aimed to enhance the dissolution rate, oral bioavailability and analgesic potential of the aceclofenac (AC) in the form of nanosuspension using cost-effective simple precipitation-ultrasonication approach. The nanocrystals were produced using the optimum conditions investigated for AC. The minimum particle size (PS) and polydispersity index was found to be 112±2.01 nm and 0.165, respectively, using hydroxypropyl methylcellulose (1%, w/w), polyvinylpyrrolidone K30 (1%, w/w) and sodium lauryl sulfate (0.12%, w/w). The characterization of AC was performed using zeta sizer, scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The saturation solubility of the AC nanocrystals was substantially increased 2.6- and 4.5-fold compared to its unprocessed active pharmaceutical ingredient in stabilizer solution and unprocessed drug. Similarly, the dissolution rate of the AC nanocrystals was substantially enhanced compared to its other counterpart. The results showed that >88% of AC nanocrystals were dissolved in first 10 min compared to unprocessed AC (8.38%), microsuspension (66.65%) and its marketed tablets (17.65%). The in vivo studies of the produced stabilized nanosuspension demonstrated that the Cmax were 4.98- and 2.80-fold while area under curve from time of administration to 24 h (AUC0→24 h) were found 3.88- and 2.10-fold greater when compared with unprocessed drug and its marketed formulation, respectively. The improved antinociceptive activity of AC nanocrystals was shown at much lower doses as compared to unprocessed drug, which is purely because of nanonization which may be attributed to improved solubility and dissolution rate of AC, ultimately resulting in its faster rate of absorption.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*

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