An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium

Ali Alaiye,Ercan Kaya,Mehmet Ozgur Pınarbaslı,Nusin Harmancı,Cafer Yıldırım,Dilek Burukoglu Donmez,Cemal Cingi 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.8

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1—physiological saline 0.9%; Group No. 2—safflower oil 100 mg/kg; Group No. 3—safflower oil 300 mg/kg; Group No. 4—benzydamine HCl 30 mg/kg; Group No. 5—benzydamine HCl 100 mg/kg; and Group No. 6—naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7–10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7—physiological saline 0.9%; Group No. 8—safflower oil 300 mg/kg; Group No. 9—benzydamine HCl 100 mg/kg; and Group No. 10—naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro–Wilk, Kruskal–Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic–anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

Ultra deformable vesicles for boosting transdermal delivery of 2-arylpropionic acid class drug for management of musculoskeletal pain

Kaul Shreya,Jain Neha,Nagaich Upendra 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.2

Purpose The aim of this investigation was to formulate and evaluate naproxen transethosomal gel for sustained transdermal delivery for the management of musculoskeletal pain. Methods In this examination naproxen sodium-loaded transethosomes were developed by ethanol injection method. A 9 run, 2-factor, 3-level factorial design was used to optimize naproxen-transethosomes. Transethosomal formulations were then incorporated into hydrogel made of gelling agent carbopol 940. The formulated transethosomes were characterized for particle size, entrapment efficiency, zeta potential, in-vitro release, ex-vivo drug permeation study, drug deposition study, and in-vivo anti-inflammatory study. Results The results exhibited that the particle size were in the range of 56.94 ± 0.12 nm to 291.7 ± 0.09 nm. The transethosomes had higher entrapment efficiency in between 66.23 ± 1.52 and 93.11 ± 0.96% and exhibited a spherical morphology when examined by TEM analysis. The in-vitro skin permeation study carried out on rat skin exhibited enhanced skin deposition with lesser systemic absorption. The in-vivo studies carried out on rats showed the superiority of naproxen transethosomal gel in reducing the edema rate. Conclusion The results obtained all together demonstrated that the formulated transethosomal gel possessed a smaller particle size, high entrapment efficiency along higher skin deposition rate which is required in getting relief from musculoskeletal pain. The developed formulation could be regarded as an ideal substitute for the conventional gel for the management of musculoskeletal pain.

Quantitative analysis and validation of naproxen tablets by using transmission raman spectroscopy

Jaejin Kim,Janghee Han,Young-Chul Lee,Young-Ah Woo 한국분석과학회 2024 분석과학 Vol.37 No.2

A transmission Raman spectroscopy-based quantitative model, which can analyze the content of a drug product containing naproxen sodium as its active pharmaceutical ingredient (API), was developed. Compared with the existing analytical method, i.e., high-performance liquid chromatography (HPLC), Raman spectroscopy exhibits high test efficiency owing to its shorter sample pre-treatment and measurement time. Raman spectroscopy is environmentally friendly since samples can be tested rapidly via a nondestructive method without sample preparation using solvent. Through this analysis method, rapid on-site analysis was possible and it could prevent the production of defective tablets with potency problems. The developed method was applied to the assays of the naproxen sodium of coated tablets that were manufactured in commercial scale and the content of naproxen sodium was accurately predicted by Raman spectroscopy and compared with the reference analytical method such as HPLC. The method validation of the new approach was also performed. Further, the specificity, linearity, accuracy, precision, and robustness tests were conducted, and all the results were within the criteria. The standard error of cross-validation and standard error of prediction values were determined as 0.949 % and 0.724 %, respectively.

Studies on the Development for Sustained Release Preparation (II):Preparation and Evaluation of Eudragit Microcapsules of Sodium Naproxen

Shin, Sang-Chul,Lee, Keong-Ran The Pharmaceutical Society of Korea 1993 Archives of Pharmacal Research Vol.16 No.1

The microencapsulation of sodium naproxen with Eudragit. RS was studied by coacrtvation/phase separation process using Span 80 in mineral oil/acetone system. Various factors which affect the mciroencapsulation, e.g., stirring speed, and surfactant concentraction, Eudagit RS concentration and loading drug amounts were examined. For the evaluation of the prepared microcapsules, release rate, particle size distribution and surface appearance as well as in vivo test were carried out. The addition of n-hexane and freezing of microcapsules accelerated the hardening of microcapsules. The optimum concentration of Span 80 ti prepare the smallest microcapsules was the same value with the CMC of Span 80 in solvent system. When 1.5% (w/w) Span 80 was used, the smallest microcapsules were formed $(30.02\pm5.05\mu$ in diameter) belonging to the powder category showing smooth, round and uniform surface. The release of sodium naproxen was retarded by microencapsulation with Eudragit RS. The Eudragit RS microcapsules showed significantly increased AUC and MRT and deceased Cl/F in rabbits.

The Crystal Structure of Naproxen Sodium, ($C_{14}H_{13}O_3Na$), A Non-steroidal Antiinflammatory Agent

Kim, Yang-Bae,Park, Il-Yeong,Lah, Woon-Ryong The Pharmaceutical Society of Korea 1990 Archives of Pharmacal Research Vol.13 No.2

The structure of the anti-inflammatory agent, naproxen sodium was determined by single crystal X-ray diffraction analysis. Crystal of the compound, which was recrystallized from methanol solution, is nomoclinic, space group $P2_1$ with a = 21. 177(6), b = 5.785(2), c = 5.443(2) $\AA, \beta$ = 91.41(3)$\{\circ}$ and Z = 2. The calculated density is 1.346; the observed value is nements based on 1093 reflections ($F\geq3\sigma$(F)) gave the final R value of 0.043. There are of one water per one compound molecule in the crystal. The carboxyl group of the molecule is nearly perpendicular to the naphthalene ring. The molecules are arranged along with the screw axis, and stabilized by five 0...Na type interactions. The molecule retains nearly same dimensions and similar conformation compared to its parent compound, naproxen, except for the torsion angles around C(5)-C(11) bond.

Formulation development and evaluation of bi layer tablets: a fixed dose combination of sumatriptan succinate and naproxen sodium as immediate release layer and sumatriptan succinate as delayed release layer

Poluri Koteswari,Srinivasa Babu Puttugunta,Gangadhar Vadlatala 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.3

Migraine is a chronic neurological disorderand characterized by splitting headaches. A combination ofsumatriptan succinate (SS) and naproxen sodium (NS) wasfound to be effective. Time to reach Cmax and biologicalhalf lives of both the drugs are different and hence optimumlevels of both the drugs cannot be maintainedsimultaneously in the blood when these drugs are administeredorally in the form of conventional tablets. Thereforethe objective of present investigation was formulationdevelopment and in vitro evaluation of a bi layer tabletdosage form containing SS and NS in a fixed dose combinationas immediate release layer and a delayed releaselayer containing SS to maintain optimum plasma levels ofboth drugs at a time and for a prolonged period. Formulationvariables for immediate release layer include sodiumstarch glycolate and cross carmellose as super disintegrantsand micro crystalline cellulose as filler. Ethyl cellulose wasused as delayed release polymer. Each layer was optimizedindividually and best compositions were selected. Usingdirect compression method bi layer tablets were preparedand evaluated. The cumulative percent drug release versustime plots of SS from bi layer tablets indicate the pattern ofdrug release. The rate of drug release followed first orderkinetics. Differential scanning calorimetry and Fourierinfrared spectroscopic studies revealed the absence ofincompatibility between drugs and excipients.

습식 과립을 통해 용해도가 개선된 나프록센 나트륨 제형 설계

이성원(Seong Won Lee),조훈휘(Hun Hwi Cho),김진우(Jin Woo Kim),김남영(Nam Yeong Kim),김필윤(Pil Yun Kim),송철의(Cheol Ui Song),이원찬(Won Chan Lee),최정민(Jeong Min Choi),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2021 폴리머 Vol.45 No.3

최근 유전 및 노화로 인해 관절염(류마티스, 퇴행성 관절염 등)으로 고통받는 환자들이 증가하고 있으며, 이들 대부분의 환자들은 지속적인 통증으로 인해 건강 관련 삶의 질(HQRL)이 저하되고 있다. 통증 치료를 위해서는 비스테로이드성 항염증제(NSAIDs)가 널리 사용되고 있으며, 대표적인 치료제로 나프록센 나트륨(NAP)이 사용된다. NAP는 발열, 염증, 통증을 일으키는 프로스타글란딘(PG)의 생성에 관여하는 효소인 사이클로옥시게나제 1과 2(COX-1, COX-2)를 억제하는 장점이 있으며, 상대적으로 반감기가 12시간이다. 그러나 NAP는 하루에 2번 275-550 mg의 경구 투여에 의해 용해도가 낮고 흡수도가 높은 생물약제학적 분류체계 c la ss 2 약물이다. 나프록센 나트륨의 낮은 용해도를 개선하기 위해 수용성 고분자인 폴리비닐피롤리돈(PVP-K30), 폴리비닐알콜(PVA), 전분과 NAP를 습식과립법으로 과립을 제조하였다. 이후 NAP의 향상된 형태와 용해도를 확인하고자 주사전자현미경(SEM), 시차주사 열량분석법(DSC), X선 회절분석법(XRD), 푸리에 변환 적외선 분광학(FTIR) 및 고성능 액체 크로마토그래피(HPLC)를 통해 확인하였다. 이러한 결과를 바탕으로 습식 과립 형성을 통해 NAP의 용해도가 향상되었음을 보여주었고, 즉시 방출 효과인 속방정으로써 관절염에 대한 치료제로 응용 가능하다는 것을 보여주었다. Recently, many patients are suffered from arthritis including osteoarthritis, rheumatoid arthritis due to increment in genetic disease and aging. Most patients with arthritis have a relatively low health-related quality of life (HRQL) due to persistent pain. For the treatment of pain, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and among them, naproxen sodium (NAP) is typically applied. NAP has merits in inhibiting cyclooxygenases 1 and 2 (COX-1, COX-2), enzymes involved in the production of prostaglandin (PG) which cause fever, inflammation, and pain, and has a relatively long half-life of 12 h. However, NAP is a biopharmaceutics classification system (BCS) class 2 drugs with low solubility and high absorption by oral administration of 275~550 mg per time, twice a day. Herein, the low solubility of NAP was improved by wet granulation of the water-soluble polymer polyvinylpyrrolidone (PVP-K30), polyvinyl alcohol (PVA), starch, and NAP. The improved morphology and solubility of NAP was confirmed by scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). Overall results showed enhanced solubility of NAP through the wet granule formation and showed promising treatment for arthritis as immediate release medicinal effects.

Preparation and release properties of naproxen imprinted allbanggae starch/PVA based biomaterials

조은비,김한성,황민진,김은식,이창문,윤순도 한국공업화학회 2021 한국공업화학회 연구논문 초록집 Vol.2021 No.-