Turkish Journal of Pharmaceutical Sciences最新文献

There are several blood-based markers to assess iron stores, but they all have some limitations. Hepcidin, a low-molecular-weight peptide hormone, is produced mainly by the liver. It is the main regulator of iron homeostasis by preventing iron release into plasma from absorptive enterocytes and macrophages. This review aims to critically assess existing data on potential role of hepcidin in diagnosis, particularly the (pre) analytical implications of the hepcidin measurement. There is a well-known causative correlation between hepcidin and iron deficiency. Therefore, hepcidin is considered as a promising marker in the assessment of iron status, particularly in patients with a diagnostic dilemma, such as patients with chronic renal disease and infants. The clinical implications of this peptide hormone in diagnosis of other diseases have been expanded in the recent studies, including elevated hepcidin levels in neoplastic diseases, sepsis, and inflammation. The potential role of hepcidin in diagnosis is controversial in the various types of iron deficiency because data are conflicting (as in anaemia of chronic disease) or limited (as in infants), whereas in the case of hereditary haemochromatosis, it has been proposed that hepcidin may be used for stratification of molecular testing, or to improve the frequency of phlebotomy, however, this issue still needs to be investigated. Due to lack of a clinically approved test, the medical application of this peptide as a biomarker in diagnosis is restricted. Recently, assays have been developed to determine hepcidin levels in serum and urine, facilitating the future use of hepcidin in research and clinical practice.

Objectives: This investigation was aimed at designing an effective mucoadhesive microemulsion system to accomplish higher brain uptake of curcumin through intranasal route.

Materials and methods: Mucoadhesive microemulsion of curcumin (MMEC) was developed using screened oil, surfactant, and co-surfactant by Box-Behnken design and was evaluated for mucoadhesion, stability, and naso-ciliotoxicity study. Comparative brain uptake of curcumin after nasal administration of MMEC and polycarbophil curcumin gel and intravenous administration of plain curcumin solution was studied by performing bio-distribution study in Swiss albino rats.

Results: The results showed that all formulation variables i.e., the amount of capmul MCM (X1), S_mix (accenon CC: transcutol P) (X2) and percentage of aqueous. Polycarbophil (X3) had a significant effect (p<0.05) on the responses. The developed MMEC was stable and non-ciliotoxic with 66.74 ± 3.46 nm and 98.58% ± 1.21 as average globule size and drug content, respectively. Polydispersibility index (0.133 ± 0.17) data and transmission electron microscopy study depicted the narrow size distribution of MMEC. Furthermore, following a comparative investigation of the brain uptake of curcumin among MMEC, plain drug gel and intravenous administration at 2.86 mg/kg, more brain uptake of curcumin was demonstrated for MMEC over intravenous application. Moreover, curcumin uptake in olfactory bulb after nasal administration of MMEC (31.11 ± 1.6) was than 9.44 times higher than intravenous injection of curcumin solution (3.25 ± 1.01). Area under curve represents the ratio of 2.86 mg/kg in brain tissue to plasma acquired afterward(s) the intranasal injection of MMEC (and it) was essentially greater than after the intravenous administration of curcumin solution.

Conclusion: Findings of the investigation revealed that optimal MMEC and intranasal route may be considered to be promising and an alternative approach for brain targeting of curcumin.

Objectives: Transdermal drug delivery as a novel drug delivery system has become a major research interest to the scientists for its controlled drug release and improved patient compliance. This study was conducted to develop an optimized transdermal patch of tramadol hydrochloride using an appropriate amount of suitable polymers. It was also planned to control the drug permeation rate from the device to achieve a sustained release pattern.

Materials and methods: Several numbers of formulations were prepared by altering the amount of excipients. Physicochemical and biopharmaceutical parameters were checked to get the optimized formulation with desired characteristics.

Results: Fourier transform infrared spectroscopy results displayed no abnormal peaks and hence concluded that the drug and polymers were compatible with each other. The minimum standard deviation values of different physicochemical parameters assured that the method of preparation was skilled to develop patches with least intra-batch variability. A higher percentage of hydroxypropyl methylcellulose (HPMC) resulted in the greater tensile strength, moisture content and water vapor transmission rate of the patches. A high folding endurance value (>200) indicated the flexibility of the prepared patches and their integrity to the skin. The transdermal patches coded as F26 containing only HPMC polymer demonstrated the desired drug permeation rate (65.51%) within 12 hours through ex vivo permeation studies.

Conclusion: The formulation coded as F26 was found to be the most optimized patch as it exhibited sustained drug permeation rate followed by higuchi diffusion kinetics, that also confirmed the capability of the formulation to exhibit matrix type drug delivery.

Objectives: Gomphandra tetrandra (Wall.) Sleumer (leaves) belonging to the family Stemonuraceae was investigated for preliminary phytochemical screening and evaluating their pharmacological activities in various pharmacological models.

Materials and methods: The crude methanolic extract was screened with different chemical reagents for the qualitative detection of different phytochemical groups. The peripheral analgesic function was determined using the acetic acid-induced writhing procedure and sedative-hypnotic behaviors were assessed using hole-board, open field, and hole-cross tests using different doses of the extract (200 mg/kg and 400 mg/kg body weight).

Results: Phytochemical screening revealed that methanolic extract of G. tetranda leaves contains steroids, gums, mucilages, phytosterols, carbohydrates, and flavonoids. The crude methanolic extract at 200 mg/kg and 400 mg/kg doses showed statistically significant activity in acetic acid-induced writhing inhibition test with 60% (p<0.01) and 76.47% (p<0.01) inhibition, respectively, compared to control. The extract also had dose-dependent substantial (p<0.01) sedative-hypnotic activities compared with diazepam in the hole-board, open field, and hole-cross tests.

Conclusion: It may be assumed that the methanolic leaf extract of G. tetrandra possesses a strong possibility of having analgesic and sedative-hypnotic activity due to the presence of bioactive compounds in its leaves. Moreover, observed results have opened a new era of in-depth research to discover the possible mechanism of analgesic and sedative-hypnotic activity.

Objectives: To develop two (titrimetric and spectrophotometric) simple, rapid, sensitive and cost-effective methods for the determination of metoclopramide (MCP) in pharmaceutical dosage forms.

Materials and methods: The titrimetric method (A) was based on the N-oxidation reaction involving the use of potassium hydrogen peroxymonosulfate and subsequent iodometric back titration of a known residual reagent. The spectrophotometric method (B) was based on derivatization of MCP with potassium hydrogen peroxymonosulfate in the presence of iodide to produce a chromogen (triiodide) with a wavelength of maximum absorption at 350 nm.

Results: Method "A" was applicable over the concentration range of 0.25-3.5 mg to end volume 10 mL. In method "B", Beer's law was obeyed over the concentration range of 0.3-3.5 μg/mL with molar absorptivity of 24600 L/mol cm. The limits of quantification were calculated to be 0.25 mg/10 mL (A) and 0.2 μg/mL (B), respectively.

Conclusion: The proposed methods were suitable for determination of MCP as a pure substance in tablets and injection.

Objectives: Obesity, which is a risk factor for diabetes, hypertension, cardiovascular diseases, and cancer, is caused serious health problems and economic costs on a global scale. Nowadays, pancreatic lipase inhibitors that cause inhibition of lipid digestion and lipid absorption are one of the limited treatment approaches for obesity. Plant-derived secondary metabolites can be used for treating obesity. The aim of this study was to research the antiobesity potential of Amaranthus albus L. (Amaranthaceae), Helichrysum compactum Boiss. (Asteraceae), Chenopodium album L. (Chenopodiaceae), and Agrimonia eupatoria L. (Rosaceae).

Materials and methods: To detect the antiobesity potentials of the plants, in vitro lipase inhibitory activity studies by spectroscopic method and quantitative analysis studies of some anti-obesity effective secondary metabolites by reversed-phase high performance liquid chromatography (RP-HPLC) technique were carried out.

Results: In vitro lipase inhibitory studies showed that all plant extracts possess lipase inhibitory effect, and the highest lipase inhibitory potential was observed for H. compactum (IC₅₀: 45.70 μg/mL ± 2.3618). According to HPLC analyses, p-coumaric acid (0.27 mg/g) in A. albus; benzoic acid (0.33 mg/g) in C. album; vanillic acid (7.32 mg/g), syringaldehyde (14.97 mg/g), quercetin (4.66 mg/g), p-coumaric acid (0.71 mg/g), and benzoic acid (3.43 mg/g) in H. compactum; p-coumaric acid (0.71 mg/g) and benzoic acid (3.43 mg/g) in A. eupatoria were detected.

Conclusion: In conclusion, H. compactum is the most remarkable natural source for the study. The fact remains that all plants may be promising candidates for treating obesity.

Objectives: Present study was to develop and evaluate gastroretentive microspheres by the solvent evaporation technique.

Materials and methods: Gabapentin and HPMC K100 were used to develop the formulations. Gastroretentive microspheres were developed by the solvent evaporation technique from the preliminary batches of gabapentin microspheres batch FMG3 were selected for factorial study.

Results: Factorial batches showed the mean particle size of the floating microsphere formulations for gabapentin (FFMG1-FFMG9) was in the range of 185.63 ± 0.13 to 510.04 ± 0.09 μm. The percentage yields of formulations FFMG1 to FFMG9 for gabapentin ranged from 53.5 ± 0.95 to 96.64 ± 0.42. The buoyancy percentage was calculated for the formulations and found that all formulations could float on dissolution medium for 12 h. The drug loading in gabapentin microspheres was found 65.29 ± 0.46 to 84.3 ± 0.44. The swelling study was found to be 756.34 ± 1.48 to 890.46 ± 0.78 for gabapentin. Batch FFMG6 and FFMC2 showed better drug release 99.1% and 99.25% respectively. The optimized formulation FFMG6 for gabapentin showed an n value 0.8474 and R² value 0.9965.

Conclusion: Optimized formulation obeys Korsmeyer-Peppas release. Scanning electron microscopy images of microspheres were spherical, discrete, and freely flowing. ANOVA for the given formulations showed p value less than 0.0500. The stability study indicated no significant changes in the microspheres. In radiographic images, floating microspheres were retained in the stomach of rabbits for twelve hours.

Objectives: Empower 3 software is important in modeling, optimization, and reducing the time of manual calculation of related substance by subtracting the baseline of a blank chromatogram from the unknown sample automatically; so, the major objective of the developed method is to introduce a new, selective, and economical high performance liquid chromatography (HPLC) and spectrophotometric method for simultaneous estimation of sodium benzoate (SDB) and cefdinir (CFR) in the presence of its degradation products.

Materials and methods: Chromatographic separation is optimized and adjusted using two methods; method (I) is characterized for separation of active pharmaceutical ingredient (CFR) in pure and dosage forms using Atlantis dC18 column [4.6 mm x 250 mm (5 μm particle size or equivalent)] with a mobile phase consisting of methanol: 0.02 M phosphate buffer solution pH 3.0 (40:60 v/v) at a flow rate of 1.0 mL/minute, injection volume 10 μL and wavelength 254 nm. Method (II) is identified for related substances in a Hichrom C18 column (15 x 0.46 cm), 5 μm particle size or equivalent, using a binary gradient consisting of solution A [0.1% tetramethylammonium hydroxide solution (pH: 5.5) with 0.1 M EDTA (1000:0.4 v/v)] and solution B (0.1% tetramethylammonium hydroxide solution (pH 5.5): acetonitrile: methanol : 0.1 M EDTA (500:300:200:0.4 v/v) using injection volume 10 μL for reversed-phase HPLC with a wavelength equals to 254 nm and flow rate 1.0 mL/min. Two ecofriendly spectrophotometric methods were successfully used to resolve the spectral overlap of drugs.

Results: Method A, the first derivative of ratio spectra spectrophotometric method (1stDD) where CFR was determined at two wavelengths 283.5 nm, 313.4 nm and SDB was determined at 216.7 nm, 235.5 nm. Method B, ratio subtraction method is performed to overcome the interference between CFR and the preservative SDB. The ultraviolet spectrum of the laboratory mixture is divided by that of CFR (20 μg/mL) as a divisor then subtracting the amplitudes in the plateau region at 250-315 nm (the constant) from that of the ratio spectrum. The zero-order spectra of SDB were obtained at 225 nm by multiplying the resulting ratio spectra by the divisor (CFR), zero order of CFR was been estimated at a wavelength value of 283 nm after multiplication of the divisor by the obtained constant.

Conclusion: The optimized method was adjusted and validated as per International Conference on Harmonization guidelines and could be easily utilized by quality control laboratories and for laboratory-prepared mixtures.

Although it is considered that cosmetics do not have side effects, studies have revealed that a significant number of consumers experience side effects. Undesirable effects arising from the use of cosmetic products have created the need for a reporting and evaluation system, which is responsible for some restrictions on the use of cosmetics ingredients and putting into cosmetic regulation effect, called cosmetovigilance. However, the new cosmetovigilance concept needs some updates to become more effective for public health. For instance, side effects related to cosmetic use have been reported more frequently recently, but this rate is still quite low. Additionally, since the current cosmetic directive does not recognize cosmeceuticals as a distinct category from cosmetics, some products named cosmetic under the laws may affect the bottom layers of dermis and cause systemic side effects. Although the manufacturers must show safety assessments to the Turkish Pharmaceutical and Medical Device Agency to get a license, after launching they do not have post-vigilance reporting to the institution, which is another problem of the system. In this review, the current cosmetovigilance system in Türkiye was discussed and some hardships encountered were criticized regarding the implementation of the system. Additionally, scientific studies are conducted on cosmetic ingredients that can have side effects and contribute to the developing cosmetovigilance concept. Because of the study, the importance of the feedback of healthcare professionals in the cosmetovigilance system, the consultancy service to be given to the consumer and patient about the contents that should be considered. Besides, there is a need for new studies to indicate the adverse reaction incidence related to cosmetics in the Turkish market. Another outcome of this review article is to understand the importance of the new regulations regarding the increase in the new active ingredients in the cosmetic market.

Objectives: The aim of the investigation was to prepare sustained release (SR) pellets of diltiazem hydrochloride employing almond gum and gelucire. The study was performed to explore the suitability of almond gum in the preparation of pellets of diltiazem hydrochloride without the use of microcrystalline cellulose and role and effectiveness of hydrophobic gelucire (43/01) in controlling the drug release.

Materials and methods: Pellets were prepared by extrusion-spheronization of the blend previously obtained by incorporation of the drug in a mixture of melted gelucire 43/01 and almond gum. A 3² factorial design was employed to study the effect of two independent variables, almond gum and gelucire, on the size, friability and drug release from pellets. Scanning electron microscopy, differential scanning calorimetry and infrared spectroscopy were performed to characterize pellets.

Results: Free flowing spherical pellets could be prepared. The 3² factorial study revealed that as the proportion of almond gum increased, the size of pellets increased, while increasing gelucire had opposite effect. The yield of pellets prepared in different formulations is in the range of 86 to 92%. The size of the pellets varied from 1128 to 1458 μ. Higher amounts of gelucire resulted in pellets with greater friability, whereas increasing the amount of almond gum yielded pellets with low friability. The pellets exhibited SR of diltiazem and the presence of gelucire in the matrix of the pellets had an enhanced sustaining effect on release.

Conclusion: Dispersion of the drug in gelucire before it was converted to pellets resulted in extended release of drug. The drug release rate changed with changes in the proportion of pellet composition. The results of the study suggest that employing gelucire (43/01) in the preparation of pellets is a useful approach in the design of SR products of highly water-soluble drug such as diltiazem hydrochloride.