No abstract

Naproxen, an anti-inflammatory drug, exhibits poor aqueous solubility, which limits the pharmacological effects. The present work was carried out to study the effect of agglomeration on micromeritic properties and dissolution. Naproxen agglomerates were prepared by using a three solvents system composed of acetone (good solvent), water (non-solvent) and dichloromethane (bridging liquid). Differential Scanning Calorimetry (DSC) results showed no change in the drug after crystallization process. X-Ray Powder Diffraction (XRPD) studies showed the sharp peaks are present in the diffractograms of spherical agglomerates with minor reduction in height of the peaks. The residual solvents are largely below the tolerated limits in the agglomerates. Scanning Electronic Microscopy (SEM) studies showed that agglomerates were spherical in structure and formed by cluster of small crystals. The agglomerates exhibited improved solubility, dissolution rate and micromeritic properties compared to pure drug. Anti-inflammatory studies were conducted in Wistar strain male albino rats and naproxen agglomerates showed more significant activity than the pure drug.Uniterms: Naproxen/micromeritic properties. Naproxen/spherical agglomerates/dissolution. Residual solvents. Ulcerogenic potential. Bridging liquid.Naproxeno, fármaco anti-inflamatório, apresenta baixa solubilidade em água, o que limita os efeitos farmacológicos. O presente trabalho foi realizado para estudar o efeito da aglomeração nas propriedades micromeríticas e na dissolução. Aglomerados de naproxeno foram preparados por meio da utilização de sistema de três solventes composto de acetona (bom solvente), água (não-solvente) e diclorometano (líquido de ligação). A DSC não resulta mostrou nenhuma mudança na droga depois de processo de cristalização. Estudos de difração de Raios X do Pó (XRPD) mostraram picos agudos nos difratogramas de aglomerados esféricos, com redução mínima dea altura dos picos. Os solventes residuais estão amplamente abaixo dos limites tolerados nos aglomerados. Os estudos de Microscopia Eletrônica de Varredura (SEM) mostraram que esses aglomerados eram de estrutura esférica e formados por grupos de pequenos cristais. Os aglomerados apresentaram solubilidade, taxa de dissolução e propriedades micromeríticas aprimoradas em comparação com o fármaco puro. Estudos anti-inflamatórios foram conduzidos em ratos Wistar albinos masculinos e os aglomerados de naproxeno mostraram atividade mais significativa do que o fármaco puro.Unitermos: Naproxeno/propriedades micromeríticas. Naproxeno/aglomerados esféricos/dissolução. Solventes residuais. Potencial ulcerogênico. Líquido de ligação.

Purpose: The main aim of the present investigation was to enhance the solubility of poorly soluble Gliclazide by nanocrystallization.Methods: In present investigation gliclazide nanocrystals were prepared by sonoprecipitation using Pluronic F68, Poly Vinyl Alcohol (PVA), Poly ethylene Glycol 6000 (PEG), Poly Vinyl Pyrrolidine (PVP K30) and Sodium Lauryl Sulphate (SLS) as stabilizers. Fourier Transform Infrared Spectroscopic study (FTIR), Differential Scanning Calorimetry (DSC) and X ray diffraction (XRD) studies were conducted to study the drug interactions. Size and zeta potential of the nanocrystals were evaluated. In vitro and in vivo studies of nanocrystals were conducted in comparison to pure gliclazide.Results: The Gliclazide nanocrystals (GN) showed mean particle size of 131±7.7 nm with a zeta potential of -26.6 mV. Stable nanocrystals were formed with 0.5% of PEG 6000. FTIR, DSC and XRD studies of nanocrystals showed absence of interactions and polymorphism. SEM photographs showed a change in morphology of crystals from rod to irregular shape. There is an increase in the saturation solubility and the percentage drug release from formulation GN5 (Optimized Gliclazide Nanocrystals) was found to be 98.5 in 15 min. In the in vivo study, GN5 nanocrystals have reduced the blood glucose level to 296.4±4.26 mg/dl in 12 hr. The nanocrystals showed lower tmax and higher Cmax values as compared to pure gliclazide.Conclusion: The prepared nanocrystals of gliclazide were stable without any drug polymer interactions. Increase in the dissolution of nanocrystals compared to pure gliclazide and significant reduction in blood glucose level in vivo indicated better bioavailability of the nanocrystals. Therefore, it is concluded that nanocrystal technology can be a promising tool to improve solubility and hence dissolution of a hydrophobic drug.

The main objective of present study was to develop a buccal mucoadhesive drug delivery system for perindopril. Perindopril buccal mucoadhesive patches were developed by solvent casting technique using hydroxy propyl methylcellulose (HPMC), polycarbophil, sodium carboxymethylcellulose (SCMC) and sodium alginate as polymers for extended release of perindopril. Glycerine and DMSO were used as plasticizer and penetration enhancer respectively. Ethanol, methanol and dichloromethane were used as solvents. FTIR and DSC studies revealed no interaction between drug and polymers. The drug content in the perindopril patches was found to be uniform. The films exhibited good physical and mechanical properties. The surface pH of all the patches was within salivary pH range. Residual solvent content in patches are below the tolerated limits. The patches were found to have an extended release of the drug upto a period of 12 hours during ex vivo permeation studies with non-Fickian diffusion mechanism. The present study demonstrated the possibility of designing a buccal drug delivery system for perindopril.

The modern drug delivery system of hydrophobic drugs presents a main challenge because of the poor aqueous solubility of such compounds. Self emulsifying drug delivery systems (SEDDS) are usually used to enhance the bioavailability of hydrophobic drugs. SEDDS can be administered orally in soft or hard gelatin capsules and form fine relatively stable oil in water (o/w) emulsions upon aqueous dilution due to the gentle agitation of the gastrointestinal fluids. From time to time so many workers have claimed different rational applications of Selfemulsifying formulation for increcing bioavailability and site-specific targeting of highly lipophilic drugs. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future. The present article gives an overview of the Composition, mechanism, advantages, disadvantages, characterization, recent advancements, patents related information of SEEDS and commercial products approved for oral transmucosal administration.

Amaç: Bu çalışmanın amacı, kendiliğinden emülsifiye edici sistemlere formüle ederek, az çözünen ilaç indometazinin (IMN) çözünürlüğünü, çözünmesini ve dolayısıyla anti-inflamatuvar aktiviteyi arttırmaktır. Gereç ve Yöntemler: Kendi kendine emülsiyon haline getirici formülasyonlar yağ olarak capmul MCM, yüzey aktif madde olarak tween 80, kosürfaktant olarak transcutol P kullanılarak hazırlandı. İlaç ve eksipiyanlar arasındaki etkileşimi bilmek için fourier dönüşüm kızılötesi spektroskopisi ve diferansiyel tarama kalorimetrisi çalışmaları yapılmıştır. Pseudo üçlü faz diyagramları, kendinden emülsiyonlaşmış bölgeyi bilmek için 1:1 ile 1:4 ve 2:1 ile 4:1 arasında yüzey aktif madde ve kosürfaktant kullanılarak oluşturulmuştur. Formülasyonlar, parçacık büyüklüğü, zeta potansiyeli, kırılma indisi, viskozite ve bulut noktası açısından değerlendirildi. İn vitro çözünme çalışmaları, pH 7.2 fosfat tamponun bir bölümünde ve dört kısım suda gerçekleştirildi. Farmakokinetik parametreler Win Nonlin yazılımı ile analiz edildi. Bulgular: Kendiliğinden emülsifikasyon 2:1, 3:1 ve 1:2 oranında surfaktan ve kosürfaktant oranlarına göre daha yüksekti ve IMN formülasyonları hazırlandı. Formülasyonlar, farklı pH ve seyreltmelerde kararlıydı. Küre boyutu, 184.1 nm ile 340.5 nm aralığındaydı, çünkü yağ, yüzey aktif madde ve ko-yüzey aktif madde karışımı oranı kürenin boyutuna farklı etkiler yapmıştır. Tüm formülasyonların globüllerinin üzerindeki negatif yük, kararlılıklarına atıfta bulunmaktadır. Optimize edilmiş formülasyon, pazarlanan ürüne kıyasla daha iyi salınım gösterdi. Optimize edilmiş Kendi Kendine Emülsifiye Edici İlaç Taşıma Sistemi'nin AUC'si pazarlanan ürüne göre önemli derecede yüksekti. Sonuç: Böylece, mevcut araştırmadan kendi kendine emülsifiye IMN sistemleri, çözünmeyi ve dolayısıyla anti-inflamatuvar aktiviteyi arttırmak için yararlı bir alternatif sağlar. Anahtar kelimeler: Öz hazırlama için ilaç dağıtım sistemi, sözde üçlü faz diyagramı, zeta potansiyel, anti-inflamatuvar faaliyet, indometazin, AUC Objectives: The objective of the present study was to enhance the solubility, dissolution and hence anti-inflammatory activity of poorly soluble drug indomethacin (IMN) by formulating into self emulsifying systems. Materials and Methods: Self emulsifying formulations were prepared using capmul MCM as oil, tween 80 as surfactant, transcutol P as cosurfactant. Fourier transform infrared spectroscopy and differential scanning calorimetry studies were conducted to know the interaction between drug and excipients. Pseudo ternary phase diagrams were constructed using surfactant and cosurfactant in 1:1 to 1:4 and 2:1 to 4:1 to know the efficient self emulsification region. The formulations were evaluated for their particle size, zeta potential, refractive index, viscosity and cloud point. In vitro dissolution studies were conducted in one part of pH 7.2 phosphate buffer and four parts of water. The pharmacokinetic parameters were analysed by Win Nonlin software. Results: The self emulsification was higher with the ratios...

No abstract

Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro or nanoemulsions containing the solubilized drug. The objective of the present work was to formulate a self nanoemulsifying drug delivery system (SNEDDS) for naproxen. Naproxen SNEDDS were formulated using Labrafac PG (Oil), Span 80 (Surfactant) and propylene glycol (Co surfactant). The developed SNEDDS were evaluated for turbidimetry, droplet size analysis, zeta potential, refractive index, viscosity, drug content and in vitro diffusion profiles. All formulations of naproxen SNEDDS showed globule size in nanometric range, good stability with no phase separation and rapidly formed clear emulsion. All formulations showed more than 95% of drug release at the end of 60 min. The SEDDS showed improved dissolution rate compared to pure naproxen. Anti-inflammatory studies were conducted in Wistar strain male albino rats and ibuprofen SNEDDS showed more significant activity than the pure drug. The study illustrated the potential of naproxen SNEDDS for oral administration and its biopharmaceutical performance.