1.Validation of A Simple HPLC-UV Method For the Quantification of Andrographolide in Self-Nano Emulsifying Drug Delivery System (Snedds) For Dissolution Study
Syukri Y, Afetma D W , Sirin M, Fajri R, Ningrum A D K, Setiawan S D, Wibowo A
This research aim to validation of a simple, rapid and accurate HPLC-UV method for the quantification of andrographolide isolated from Andrographis paniculata
Ness in Self Nano Emulsifying Drug Delivery System (SNEDDS) formulation during the dissolution test. The assay was performed using a XTerra® MS C18 column (150 mm X 4.6 mm, five μm) with a mobile phase of methanol and water (70: 30), at 0.8 mL/min flow rate and UV detection of 229 nm. Simulation gastric fluid (SGF) and intestinal fluid (SIF) were prepared as dissolution medium. The validation parameter was conducted including the test on linearity, precision, accuracy, LOD, and LOQ. The result showed an excellent linearity with r = 0.999 and good selectivity for both medium dissolution. The method showed sufficient precision, with a relative standard deviation (RSD) smaller than % Horwitz. The accuracy reported as % recovery was found to be 102.61 and 101.17 % in each SGF and SIF dissolution medium. LOD and LOQ were found 0.46 and 1.40 in SGF medium, 0.87 and 2.64 in SIF medium. In conclusion, the HPLC method developed showed specificity and selectivity with linearity in the working range, good precision and accuracy and suitable for quantification andrographolide in SNEDDS formulation.
2. Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam
Shirisha Suddala, S K Sahoo, M R Yamsani
Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro
drug release studies, water uptake and erosion studies, floating behaviour and in vivo
radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo
radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.
3. Formulation and Optimization of Immediate Release Pellets of Antiplatelet Drugs Using Design of Experimentation
Deshkar S S, Pore A R
Platelets play an important role in hemostasis during tissue injury, which blocks the defect and terminates blood loss. Platelet aggregation inhibitors are widely used in treatment of cardiovascular disorders and Peripheral arterial disease. Clopidogrel bisulphate and Cilostazol, are FDA approved BCS class II drugs, used in treatment of Platelet aggregation, peripheral arterial disease and intermittent claudication. The aim of the present study was to develop an immediate release pellets for combination of Clopidogrel bisulphate and Cilostazol using extrusion spheronization technique. The effects of spheronization speed(X1
) and binder concentration (PVP K30) (X2
), on size of pellets, disintegration time and drug release were studied using 32
full factorial design. The surface response and counter plot were drawn to facilitate an understanding of the contribution of the variables and their interaction. From the results, speed of spheronization of 1100 rpm and 5% concentration of PVP K30, were selected. In vitro
drug release studies revealed more than 80% of clopidogrel bisulphate release and more than 75% of cilostazol release within 30 min of dissolution which complied with the pharmacopoeal limits. Film coated pellets did not show significant change in the drug release. DSC and FTIR studies revealed no interaction of drugs and excipient during pellet formulation. The pellet formulations of clopidogrel and cilostazol were found to be stable when stored at 40ºC±2ºC/ 75%RH±5%RH for 2 months. Conclusively, clopidogrel bisulphate and cilostazol pellet fixed dose combination could be successfully developed by design of experimentation and complied with pharmacopoeal limits.
4. Liposomes: Current Approaches for Development and Evaluation
Ashutosh Gupta, Surajpal Verma, Bhupendra Singh, Yashwant, Bharat Jhanwar
Liposomes (50-1000nm) are the part of a specific type of drug delivery system which is non-toxic and biodegradable in nature. That having ability to reduce the toxicity also enhances the therapeutic efficiency and protects the drug which is encapsulated, from the degradation and immediate dilution. These can be prepared by using various techniques like lipid hydration method, sonication method and solvent injecting method etc. But the selection of technique is depended upon the size of liposome which we want. The main disadvantage of this dosage form is it is very much costly and also having time consuming process. But it has major applications in the form of extrusion for homogeneous size, long circulating liposomes, triggered release liposome, remote drug loading, ligand targeted liposomes and containing combination of drugs. These applications are helpful for advanced drug delivery of anticancer, antifungal and anti-inflammatory drug, the delivery of gene medicine, delivery of anaesthetic and antibiotic drug. The newer researches in this field include hybrid liposomes, phototrigerable liposomes which are fabricated to have the improved functionality. These serves as the upcoming novel nanomedicinal chemotherapy technique.
5. Chitosan-Based Hydrogel Nanoparticles for Cancer Therapy
Azadi A, Khazaei M, Bashiri R, Ashrafi H
Cancer, an uncontrollable growth of cells, is among the leading causes of mortality and morbidity throughout the world. Malignant neoplasms are difficult to treat diseases because of their single in kind characteristics such as tissue invasion, metastasis, evading reticuloendothelial system (RES) and so forth. In recent decade polymeric nanoparticulate systems has gained special attention in drug delivery and targeting among all biocompatible nanoforms. Among these systems, chitosan-based hydrogel nanoparticles have been wildly utilized for drug delivery purposes. The usage of chitosan nanogels in cancer therapy significantly improved in recent years. The various cancers were the target of chitosan nanogels. Also, modification of other delivery systems with chitosan were much reported. The aim of this study is the review and update of the recent studies on chitosan nanogels applications in cancer therapy by focus on cancer based classification.
6. Proniosomes as Nano-Carrier for Transdermal Delivery of Atenolol Niosomal Gel
El-Assal M I A
Objective of the study is to prepare Proniosomes that refers to a flexible vesicular carrier with the potential for drug administration through the transdermal route. Medthod: Proniosomes were prepared by the coacevation-phase separation technique The prepared formulations were evaluated for vesicle size, entrapment efficiency. The optimal poniosomes formula (A8) was prepared with different aqueous phase, incorporated in a gel base and studied for pH, viscosity, spredapility, stability, in vitro
drug release and ex vivo
permeation. Results: Niosomes formulations prepared with Span 40 and 60 have spherical and smaller Nano size. 25 mg atenolol loading has resulted 190.9 ± 15.033 nm sizes. EE% of the optimum formula prepared with distilled water was 62.11 to 92.38 .Rheological behavior showed combined shear thinning and thixotropic and gel was spreadable . Tested formulations were stable on cooling (4-8 o
C) . In vitro
drug release followed zero order kinetic, and gave sustained release. Release rate was significantly higher across cellulose membrane compared with rate skin. Amount of drug obtained after skin extraction was 92.6 ± 0.5% indicate enhanced permeation rate. Conclusion: All the proniosomal gel formulations were found through the acceptable range of vascular size and entrapment efficiency. Formulation A8 has been selected as an optimized therapeutic system of atenolol.
7. A Review on Novel Drug Delivery System: Microsponges
Soumya Singh, Dherendra Sahu
Recent research on idealizing drug delivery system which is progressing at a prodigious rate and aims at development of drug delivery system (DDS), with maximum therapeutic advantages of drug delivery, thus resulting in safe and effective management of disease. More and more developments in delivery systems are being integrated to optimize the efficacy and cost effectiveness of the therapy. New classes of pharmaceuticals, biopharmaceuticals are fueling the rapid evolution of drug delivery technology. Microsponge technology has been introduced in topical drug products to facilitate the controlled release of active drug into the skin in order to reduce systemic exposure and minimize local cutaneous reactions to active drugs. Microsponge consists of microporous beads loaded with active agent. When applied to the skin, the microsponge releases its active ingredient on a time mode and also in response to other stimuli (rubbing, temperature, pH etc.) that are used mostly for topical and recently for oral administration Microsponges are porous, polymeric microspheres that are mostly used for prolonged topical administration. Microsponges are designed to deliver a pharmaceutically active ingredient efficiently at minimum dose and also to enhance stability, reduce side effects, and modify drug release profiles. Microsponges are prepared by several methods utilizing emulsion system or by suspension polymerization in a liquid–liquid system. The most common emulsion system used is oil-in-water (o/w), with the microsponges being produced by the emulsion solvent diffusion (ESD) method. Microsponge delivery system (MDS) can provide increased efficacy for topically active agents with enhanced safety, extended product stability, enhanced formulation flexibility, reduced side effects and improved aesthetic properties in an efficient and novel manner. In addition these are non-irritating, non-mutagenic, non-allergenic, and nontoxic. The present review introduces microsponge technology in great detail.
8. Improvement of Dissolution Properties Through Acyclovir – Succinic Acid Cocrystal Using Solvent Evaporation Technique
Hilya Nur Imtihani, Agnes Nuniek W, Dwi Setyawan, Esti Hendradi
The objective of this research was to prepared acyclovir cocrystals with succinic acid as coformer using three different solvents (ethanol, acetic acid glacial, and 0.1N HCl) to influence the characters and improve the dissolution rate of acyclovir. Cocrystallization of acyclovir with succinic acid as coformer was successfully prepared by solvent evaporation technique using three different solvents (ethanol, acetic acid glacial, and 0.1N HCl). The screening indicated that acyclovir formed novel cocrystals with succinic acid in the three different solvents. PXRD profile show that there is three peaks in ethanol cocrystal in angle 2θ 5.9134o
. For acetic acid glacial and 0.1N HCl cocrystal there is one peak in angle 2θ 5.9263o
and 2θ 9.6011o
. In analysis diffractogram DSC formed ethanol cocrystal with melting point 175.84o
C. The melting point of acetic acid glacial cocrystal is 178.41o
C and 0.1N HCl cocrystal is 156.75o
C. The dissolution rate of the cocrystals measured by the effisiency disolution (ED45
) that considerable faster than that pure acyclovir and the physical mixtures. On the result of FTIR analysis there is changes of the wavenumber that indicated that there is cocrystal formed. And for SEM analysis, morphology of cocrystals was different than the original materials. In dissolution test, ethanol and acetic acid glacial cocrystals have better efficiency dissolution (ED45
) (92.96 %) than the acyclovir ED45
(84.48 %). But 0.1N HCl cocrystal has lower ED45
than acyclovir that is 48.19 %. The results obtained in this research indicated the acyclovir cocrystals have formed with succinic acid as coformer using three different solvents. The physical properties was different from the three cocrystals. Dissolution rate of acyclovir cocrystals using ethanol and acetic acid glacial solvents was increase, whereas using 0.1N HCl was decrease rather than pure acyclovir.
9. Solvent Concentration Effect on Powder X-Ray Diffraction and Dissolution Profiles of Acyclovir-Nicotinamide Cocrystals
Setyawan D, Siswandono
, Winantari A N, Zu’aimah K
Objective : Acyclovir (ACV) is well-known antiviral agent that has absorption problem, mainly due to its poor solubility in water and oral bioavailability. To improve acyclovir physical properties, especially dissolution properties, acyclovir-nicotinamide(NCT) cocrystal was formed. Methods : ACV-NCT cocrystal was prepared using slurry method using ethanol as solvent with different concentration. The ACV-NCT cocrystal from each sample groups was characterized using powder X-ray diffraction (PXRD), and then dissolution properties evaluated. Results : Each ACV-NCT cocrystals prepared from slurry method with different ethanol concentrations have different PXRD profile. Dissolution analysis (ED15
) showed that ACV-NCT cocrystallization using slurry methods with 10,0 ml/g as ethanol concentration significantly increase ED15
values compared to acyclovir and acyclovir-nicotinamide physical mixture (α=0,05). Conclusion : ACV-NCT cocrystal successfully formed using slurry method with 10,0 ml/g as optimal ethanol concentration.
10. Self-Nanoemulsifying Drug Delivery System (SNEDDS) with Enhanched Solubilization of Ethanol Extract from Mangosteen Peels (Garcinia Mangostana, L.) for Treatment of Topical Gangrene Foot: Design and Optimization
Pratiwi L, Sari R, Apridamayanti P
The aim of the present study is to develop and optimize self-nanoemulsifying drug delivery systems (SNEDDS) to improve the topical bioavailability of poorly soluble ethanol extract of mangosteen peels and to get optimum method of SNEDDS by simplex lattice design, using Design Expert software ®version 7. Solubility of ethanol extract of the mangosteen peels was estimated in various compositions to select proper components combinations. Virgin coconut oil/ VCO (oil), Tween® 80 (surfactants) as well as polietilenglikol 400 (PEG 400) (co-surfactants) were employed to construct pseudo-ternary phase diagrams. Transmittance and pH, droplet size, zeta potential, and thermodynamic stability were performed to optimize formulations from phase diagram. Fourteen formulations composed of VCO, Tween 80 and PEG 400 at simplex lattice design ratios were selected. The results showed that the ethanol extract of the mangosteen peels SNEDDS optimum consisting of Cremophor EL as the surfactant, PEG 400 as the co-surfactant, and VCO as the oil phase with a ratio of 5.27: 1: 1.72. Evaluation of SNEDDS with an optimum formulation with drug loading value of 125 mg/5 mL, emulsification time of 5,2 seconds, transmittance value of 74,6552 %, pH value 5,85 and has a particle size of 18,9 nm. Ethanol extract of the mangosteen peels loaded SNEDDS, with enhanced solubilization and nanosizing, and has potential to improve the absorption of drug and increase its topical antimicrobial activity against Staphylococcus aureus.
11. Chitosan/Silk Sericin Blend Microparticles Prepared by Water-in-Oil Emulsification-Diffusion for Controlled Release of Silk Sericin Antioxidant
Theeraphol Phromsopha, Yodthong Baimark
This study aimed to develop the novel drug delivery carriers to control the release of silk sericin antioxidant. The chitosan/silk sericin blend microparticles were successfully prepared by the water-in-oil emulsification-diffusion method. Influence of silk sericin ratio on characteristics and in vitro
silk sericin release behaviors of the blend microparticles was investigated. All the spherical-shaped blend microparticles had an average size of 41 – 48 mm and could load the silk sericin in high loading efficiency (69 – 75%). The FTIR and thermogravimetric results indicated the blend microparticles with different silk sericin contents can be prepared by varying the silk sericin feed ratio. The blend microparticles exhibited sustained release profiles of the silk sericin. The in vitro
silk sericin release content increased as the silk sericin ratio increased. Antioxidant activities of the blend microparticles assessed by FRAP assay were more than the neat chitosan microparticles and steadily increased with the silk sericin ratio. The results demonstrated that the chitosan/silk sericin blend microparticles prepared by the water-in-oil emulsification-diffusion method should be useful drug delivery carriers for the controlled release silk sericin antioxidant.
12. Anti-Inflammatory Evaluation of NLC (Nanostructured Lipid Carriers) Meloxicam In-Vivo
Widyaningrum I, Hariyadi D M, Hendradi E
Objective : The aim of this research study was to investigate the anti-inflammatory effect of NLC meloxicam. NLC contains solid and liquid lipid. Monostearin as solid lipid and Miglyol 808 as liquid lipid. Methods : NLC meloxicam was repared using emulsification methodwith three different lipid ratio. . NLC meloxicam was prepared and characterized for measuring the pH, viscocity, particle size, and entrapment efficiency. The rat paw edema test was performed to evaluate the anti-inflammatory activity of three formulations NLC meoxicam. Results : based on research result shows that the smaller the solid lipid concentrations, particle size is the larger, the greater viscosity, thus increasing occlusive NLC to the skin. The third formula hasthe greatest solid lipid concentration shows the smallest AUC value but once in a statistical test known to be significantly different from the three formulas. Conclusions : NLC meloxicam showed that it had anti-inflammatory effectiveness.
13. Design and Development of Clobetasol Propionate Topical Gel Thickened with Novel Copolymer
Kumar Pawan, Singh Shailendra Kumar
Topical delivery of clobetasole propionate (CP) offers several formulation related problems due to poor water solubility and photo degradation property. In the present investigation, topical gel of CP was formulated using Acrylamide/ Sodium Acryloyldimethyl taurate copolymer (SEPINEO™ P 600) as a gelling agent and evaluated with respect to different physicochemical parameters such as pH, viscosity, bio-adhesivity, spreadability, in vitro drug release and photo stability. Permeation of CP gel was studied using freshly excised pig ear skin for 24 h. The cumulative permeation of drug through excised rat skin was 3.0 ± 1.2 mg cm-2
with the corresponding flux value of 0.24 ± 0.09 mg cm-2
. The in vitro
release studies showed 101.43±1.12 % drug release over 10 h. The selected formulation was found to be effective with respect to percent drug content, permeation characteristics, pH, viscosity, and photostability. Therefore, CP gel could be very promising alternative for the topical drug delivery.