Percentage Drug Research Articles

Design and evaluation of floating microspheres of ranitidine HCL

In recent years oral dosage form for gastric retention (floating drug delivery systems) has drawn increasingly more consideration for their theoretical convenience in permitting control over time and site of drug release. The present study intended to develop floating microspheres of Ranitidine HCL, which belong to the class of Histsamine2 blockers. Floating microspheres Ranitidine HCL was prepared by the emulsion solvent evaporation method using HPMC K15M and ethylcellulose as polymer. Six different formulations were developed. The floating microsphere was assessed for the angle of repose, particle size, percentage yield, in vitro lightness, manifestation efficiency, drug-polymer compatibility (IR-study), scanning electron microscopy, drug release and DSC (Differential Scanning Colorimetry), X-Ray Diffraction (XRD) of the microsphere. The outcome of the experiment shows that as the concentration of polymer influences its result the particle size, percentage yield, in vitro buoyancy and drug release of the microsphere. Formulations produced with HPMC K15M exhibited superb Micromeritic properties, percentage yield, in vitro buoyancy, manifestation efficiency, and percentage drug release when contrasted with ethylcellulose polymer. Consequences of our present study propose that the floating microsphere of Ranitidine HCL can be effectively intended to develop controlled drug delivery which can lessen dosing recurrence thus this formulation can be considered as an alternative to conventional dosage forms.

In vitro and in vivo evaluation of gentamicin sulphate-loaded PLGA nanoparticle-based film for the treatment of surgical site infection

The study focuses on the in vitro and in vivo evaluation of the developed gentamicin sulphate (GS)-loaded poly lactic-co-glycolic acid (PLGA) nanoparticle (PNP)-based pullulan film (PNP-F). Sterilization being an essential pre-requisite for the dosage form was carried out using ethylene oxide. Post-sterilization, PNP-F was evaluated for mechanical properties, percentage drug loading, antimicrobial effectiveness study, test for sterility and in vitro dissolution study using Strat-M® membrane. In vitro dissolution study revealed that GS gradually released from PNP-F and the highest cumulative percentage drug release was found to be 86.76 ± 0.03% at 192h. Wound healing assay was performed to study the effect of PNP-F over migratory potential of dermal fibroblast cells (NIH-3T3) in the presence of micro-organisms, Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). PNP-F inhibited the growth of PA and SA, allowing the growth of fibroblast cells indicating its suitability for application. In vivo study of surgical site was performed by superficial incision model in Wistar rats. Measurement of in vivo incision healing confirmed faster wound healing in the incision which received PNP-F compared to marketed cream containing GS. Graphical abstract.

The use of new quinazolinone derivative and doxorubicin loaded solid lipid nanoparticles in reversing drug resistance in experimental cancer cell lines: A systematic study

The aim of this research is to study the feasibility of using carnauba wax as a new carrier for anticancer agents to deliver doxorubicin (DOX) as a model drug and a novel quinazolinone derivative (QZO-DER) to different types of normal and resistant cancer cell lines. A Box-Behnken design was implemented to investigate the influence of high melting point carnauba wax stabilized with cell membrane lipid (lecithin) and non-ionic biocompatible surfactant (span 60) in different concentration on particle size, entrapment efficiency of each drug and percent drug release. The solid lipid nanoparticles (SLNPs) were produced via the hot-melting homogenization technique. SLNPS particle size was from 16.58 ± 4 to 72.45 ± 1.21 nm and from 7.93 ± 1.67 to 174.31 ± 4.86 nm for DOX and QZO-DER respectively. Entrapment efficiency was from 51.78 ± 1.68% to 92.52 ± 2.47% and from 50.21 ± 1.8 to 82.95 ± 3.56% for DOX and QZO-DER respectively. While the percentage of release after 36 h was from 29.28 ± 3.89% to 78.08 ± 3.78% and from 37.5 ± 1.09 to 100 ± 1.25% for DOX and QZO-DER respectively. Selected formulations for DOX (OFX1 and OFX4) and QZO-DER (OFR4 and OFR6) were generated after validation of design. The in vitro anticancer activity was tested against both a panel of wild type and DOX-resistant human cancer cell lines. Cancer cell lines included colorectal cancer (HCT-116), breast cancer (MCF-7 and MDA-231), and lung adenocarcinoma (A549). Most of the tested SLNPs improved the efficacy of QZO-DER and DOX against the different cancer cell lines and have extended the spectrum to cover those accruing resistance during chemotherapy. QZO-DER loaded SLNPs exhibited the highest ability to reverse the drug resistance of MDA-231 cells compared to MDA-231/ADR cells was 19.7-fold, while DOX loaded SLNPs that showed reversal power was 1.8 fold for the same cells. Additionally, SLNPs showed a broad safety margin in normal cells. This study presented the use of SLNPs with carnauba wax as a potential therapeutic strategy to improve anticancer activity and overcome cancer resistance for clinical use.

Comparison of In-Vitro Dissolution of Griseofulvin Tablet made from Nano Particles and Solid Dispersion

Objectives: To find out the comparison of dissolution results of griseofulvin tablets made from nanoparticles, solid dispersions, and conventional materials.
 Interventions: Different types of active ingredients in the form of nanoparticles and solid dispersions can affect the dissolution results of tablets.
 Main outcomes measure: The results obtained in this study are the cumulative dissolution percentage and the order kinetics of the release of active ingredients.
 Conclusion: There was no significant cumulative percent drug release difference (p> 0.05) between nano particles, solid dispersions, and conventional materials. Tablets containing active nanoparticles, solid dispersions, and conventional materials show a linear relationship with a correlation coefficient (R2) close to 1, shown in zero-order kinetics models.
 

Functionalization of ginger derived nanoparticles with chitosan to design drug delivery system for controlled release of 5-amino salicylic acid (5-ASA) in treatment of inflammatory bowel diseases: An in vitro study

The present study aimed at synthesising chitosan bound ginger nanocarriers for slow and controlled release of the drug 5-amino salicylic acid (5-ASA) against inflammatory bowel diseases (IBD). The chitosan, extracted from naturally occurring biopolymer chitin, was reacted to ginger extract (Zingiber officinale) to prepare chitosan-bounded ginger derived nanocarriers (C-GDNC) and further loaded with 5-ASA drug. The as-obtained drug loaded chitosan coated ginger derived nanocarriers (D-C-GNDC) were studied for controlled release of 5-ASA. In vitro experimental data implied slow and controlled release of 5-ASA and were kinetically justified by applying different kinetic models. The obtained percent drug loading capacity and entrapment efficiency were more than 50%. Various experimental factors affecting swelling controlled drug release of 5-ASA, such as change in pH of release medium, chemical composition of nanocarriers, percent drug loading, and simulated biofluids as release media, were investigated. The prepared nanomaterials were well characterized and examined for chemical stability and in vitro cytotoxicity to check their biocompatible nature. The overall studies concluded that the controlled release of 5-ASA was favourable at the gastrointestinal pH which is desirably beneficial against inflammation of bowl.

Simplification of fused deposition modeling 3D-printing paradigm: Feasibility of 1-step direct powder printing for immediate release dosage form production.

Direct powder three-dimensional (3D)-printing (DPP) of tablets to simplify fused deposition modelling (FDM) was explored. The FDM paradigm involving hot-melt extrusion for making 3D-printable drug-loaded filaments as intermediate products for tablet manufacturing has been gaining attention for the decentralized on-site production of personalized dosage forms. For direct 3D-printing, powder blends were loaded into a cartridge-like head and were successfully printed with honeycomb design following heating of the extrusion cartridge. This 1-step DPP with incorporation of in-built porosity providing higher surface area served as proof of concept for manufacture of rapid release dosage forms. Water soluble hydroxypropylcellulose SSL was chosen as matrix former and caffeine as model drug. The effect of PEG4000 as plasticizer/pore former and Kollidon VA64 as rapidly dissolving polymer on DPP processability and dissolution rate was investigated. Directly 3D-printed tablets with low (30%) infill density showed rapid dissolution independently of the formulation, whereas for high (80%) infill density a combination of PEG4000 and Kollidon VA64 was required to achieve rapid release. The obtained tablets demonstrated good uniformity of percent drug content but had variable weight. Caffeine was present in crystalline state and in the stable polymorph in the tablets. Hence, DPP feasibility for immediate release dosage form manufacture was demonstrated. This technique might create an opportunity to avoid hot-melt extrusion allowing 3D-printing independently of mechanical properties of a filament and potentially prolonging product shelf life by reducing thermal stress.

Novel Approach for Transdermal Delivery of Rifampicin to Induce Synergistic Antimycobacterial Effects Against Cutaneous and Systemic Tuberculosis Using a Cationic Nanoemulsion Gel.

PurposeThis study demonstrated improved transdermal delivery of rifampicin-loaded cationic nanoemulsion gel to treat systemic and cutaneous tuberculosis using capmul, labrasol, and acconon, which exert anti-Mycobacterium activities. This approach enhanced drug permeation across the skin, increased therapeutic efficacy, and reduced dose-related side effects.MethodsDesign Expert® was used to optimize formulations (Smix ratio and capmul as independent factors), which were prepared using a slow spontaneous titration method. The optimized nanoemulsion was incorporated into carbopol gel to allow for topical application and comparative assessments. Nanoemulsions and gels were evaluated for size, size distribution, shape, zeta potential, percent spread, viscosity, in vitro hemolysis, in vitro release, and ex vivo skin permeation and deposition. A mechanistic evaluation was performed using scanning electron microscopy. Furthermore, in vivo pharmacokinetic and irritation studies were performed.ResultsThe optimized cationic nanoemulsion (OCNE-1) was characterized by small particle size (≤100 nm), had optimal viscosity, percent spread, zeta potential, and percent drug release, and was hemocompatible. The OCNE-1T gel exhibited higher permeation flux (51.32 ± 0.5 µg/cm2 hr), permeation coefficient (2.566 ± 0.08 cm/hr), drug deposition (994.404 µg/cm2), and enhancement ratio (7.16) than those of the OCNE-1 nanoemulsion or drug solution. Scanning electron microscopy was used to characterize the mechanism of enhanced permeation. An In vivo study showed that the Cmax and area under the curve following transdermal application were 4.34- and 4.74-fold higher than those following oral administration.ConclusionTransdermal delivery of rifampicin could be a promising alternative to conventional approaches to treat systemic and local tuberculosis, and other bacterial infections.

Preparation of mucoahesive tablets of famotidine by wet granulation method and its in-vitro testing

Objective: Famotidine is a histamin H2-receptor antagonist.The aim and objective of the present work is toformulate and evaluate mucoadhesive tablets of famotidine. It is also foused on the selection of mucoadhesivepolymer & its activity in various combinations & ratios. The poor bioavialability & shorter half-life suffice thedevelopment of controlled release mucoadhesive formulation. Method: Mucoadhesive tablets each containing 20mg of famotidine were prepared by conventional wet granulation method employing as mucoadhesive materials. A batch of 50 tablets was prepared, in each case a blend of 1 gm of famotidine with different polymers addition indifferent strengths with required 40mg lactose as diluent achieved after titration which were then grannulated along with a solvent blend if water and ethyl alcohol. Results: The flow properties of all five batches were in between fair and passable. Hardness of tablets ranged from 6.9-8.2 kg/cm2 and the percentage friability was between 0.25-0.79 %. The drug content uniformity in the mucoadhesive tablets was 96.49-104.81%. The surface pH study was within the range from 6.7-7.4. From all formulations, over 20% of the famotidine was release within first hour of dissolution study. In the present study the formulation FT04 (tragacanth & HPMC ) has shown cumulative percent drug release of about 80.762% in 12 h. Conclusion: From the results we concluded that formulation containing famotidine with HPMC & tragacanth has given better drug release property than the other four formulations & the wash-off test has shown that this formulation (FT04) has better mucoadhesive property.

FORMULATION AND EVALUATION OF CHLOROTHALIDONE LOADED MOUTH DISSOLVING FILM-A BIOAVAILABILITY ENHANCEMENT APPROACH USING MULTILEVEL CATEGORIC DESIGN

Objective: The intension of the present study includes fabrication and optimization of mouth dissolving film loaded with Chlorothalidone by solvent evaporation techniques using two components and their three levels as multilevel Categoric design.
 Methods: Major problem associated with the development of film loaded with BCS class II drug is to increase its solubility. Here the Chlorothalidone solubility achieved by co-solvents, such as methanol. After dissolving the drug in co-solvent, this drug solution is poured into an aqueous dispersion of Hydroxypropyl Methylcellulose E5 (HPMC E5) and Polyethylene glycol 400 (PEG 400). The two independent variables selected are factor A (concentration of HPMC E5) and factor B (concentration of PEG 400) was selected on the basis of preliminary trials. The percentage drug release (R1), Disintegration time in sec (R2) and folding endurance (R3) were selected as dependent variables. Here HPMC E5 used as a film former, PEG 400 as plasticizer, mannitol as bulking agent, Sodium starch glycolate as a disintegrating agent, tween 80 as the surfactant, tartaric acid as saliva stimulating agent, sodium saccharin as a sweetener and orange flavour etc. These fabricated films were evaluated for physicochemical properties, disintegration time and In vitro drug release study.
 Results: The formulation F6 has more favorable responses as per multilevel categoric design is % drug release about 98.95 %, average disintegration time about 24.33 second and folding endurance is 117. Thus formulation F6 was preferred as an optimized formulation.
 Conclusion: The present formulation delivers medicament accurately with good therapeutic efficiency by oral administration, this mouth dissolving films having a rapid onset of action than conventional tablet formulations.

Formulation and evaluation of neem extract hand sanitizer

Objective: The present research has been undertaken for the formulation and evaluation of neem Extract of hand sanitizer. It is used for topical use for the local anaesthetic activity. Methods: Carbopol 934 was used as a polymer in various batches. The ratio of Carbopol 934 was changed for various batches. Developed Formulations of Physicochemical parameters such as percentage yield, drug content, pH, Viscosity, Spreadability, Extrudability and In-vitro Diffusion study were carried out for developed batches of Neem extract. Results: Viscosity studies of various formulations Exhibited that Formulation F3 was better than that of F1 and F2. From among all the developed formulation, F3 Shows better rheological properties and excellent Extrudability. pH of the F3 Batch is Sufficient to treat the bacteria. Percentage yield and drug content of F3 batch is better than other batches. Results shows that the concentration of Carbopol 934 gives the good rheological properties and drug contents. In-vitro Diffusion studies were carried out, F3 batch shows better results than that of the other two batches i.e. 99.06%. Conclusion: It was concluded that F3 batch is the better than that of other batches. So F3 batch is better for the topical use.

Formulation and Evaluation of Celecoxib loaded colon Targeted Microsponges

The present research work support preformulation, formulation, development and optimization of colon targeted microsponges containing Celecoxib as a nonsteroidal anti-inflammatory drug. The different batches of formulation were evaluated using celecoxib as active pharmaceutical ingredient, Eudragit as the pH sensitive polymer, polyvinyl alcohol and triethyl Citrate. Colon targeted microsponges of Celecoxib were prepared by Quasi-emulsion solvent diffusion method. The prepared formulations were evaluated for various parameters like Particle size, Percentage entrapment efficiency, Measurement of Zeta Potential, FTIR, in-vitro release study. The result were found to be within standard limits. FTIR study reports indicated that there was no interaction between Celecoxib and other excipients. Zeta Sizer shown that the microsponge size ranges from 61.12 μm to 67.59μm. Percent drug content was between 65.18%– 95.19%. Based on the resultants of the entrapment and particle size of microsponges, formulation M4 was observed to be optimized formulation. The optimized formulation exhibited 71.52% cumulative drug release after 10 h. The optimized batch shows 77.40% yield.

Development of Multiparticulate Oral Dosage Form of Zopiclone

The aim of the present study is to develop and evaluate immediate release zopiclone pellets by using the extrusion-spheronization technique for treatment of insomnia. Immediate release pellets of zopiclone were prepared by using sodium starch glycolate (SSG) and HPMC E-5 as disintegrant and binder respectively along with microcrystalline cellulose (MCC) as a spheronizing aid, corn starch and lactose (monohydrate)as fillers. Pellet formulation was further optimized for disintegration time and percent drug release after 45 min. using 32 factorial design. There was no interaction between drug and polymer by FT-IR study. The zopiclone pellets batch (F7) prepared with SSG (4%) and HPMC E-5 (2%) spheronized at 850 RPM was found to be optimized. The optimized batch showed narrow particle size, less disintegration time and immediate drug release of 94.8% after 45 min. For treatment of insomnia, immediate release zopiclone pellets formulated in this study, can serve as an alternative to tablet dosage form.

Development and Characterization of Colon-targeting 5-Fluorouracil Multiparticulate Beads

This investigation is related to the development and optimization of multiparticulate beads of fenugreek seed mucilage-sodium alginate containing 5-flurouracil through ionotropic gelation technique using 32 full factorial design generated with Design-Expert® Version11 software. The beads were developed using CaCl2 as the crosslinking agent. The effect of ratio of fenugreek seed mucilage and sodium alginate blend and concentration of CaCl2 on the drug encapsulation efficiency, bead size and percent cumulative drug release in 6 h was optimized by 32 factorial design. The beads were also characterized using field emission scanning electron microscopy, Fourier-transform infrared spectroscopy and thermal analysis. The percent drug encapsulation efficiency of all these beads was within the range of 43.91 to 85.39 % with an in vitro drug release of 33.92 to 39.23 % in 6 h. The optimized batches of beads were coated with Eudragit S100 (5, 10 and 15 % w/v) to facilitate colon targeting in a prominent way. The in vitro drug release from the coated beads (P3) in various colonic fluids followed zero-order pattern with erosion mechanism in 18 h. The average size of these beads was within the range of 895 to 1021 μm. The optimized fenugreek seed mucilage-alginate beads containing 5-flurouracil showed significant drug permeability over a prolonged period in an ex vivo permeability study through goat colon. The results indicated successful colon targeting of 5-flurouracil multiparticulate beads developed using polymeric blends containing sodium alginate and fenugreek seed mucilage in an appropriate ratio.

Development of Mouth Dissolving Films of Ondansetron Hydrochloride By Using Factorial Experimental Design

The objective of this study was to develop a mouth dissolving film of ondansetron hydrochloride, an antiemetic drug that can not only serve in an active form but also provide rapid relief from motion sickness. Mouth dissolving oral film of ondansetron hydrochloride is a novel dosage form and was prepared by using HPMC E5, HPMC E15 and PVP K30 as a film-forming polymer in different concentrations. To study the effect of independent variables, i.e., concentration of HPMC E5, HPMC E15, and PVP K30 on various dependent variables like disintegration time and percentage drug content, 33 factorial designs was employed by using Design expert .11 After the application of 33 factorial experimental design, the process was optimized for the response variables R1-R2. The formulation showing disintegration time in the range (10-30 second), desired percentage drug release more than 85% is selected as optimized formulation. Formulation mouth dissolving films-5 (MDF-5), MDF-8, MDF-14, MDF-20, MDF-24, and MDF-25 shows desirable characteristics; all these formulations were taken as optimized formulation and subjected to in vitro dissolution study. MDF-25 containing 1% HPMC E5, 1% HPMC E15, and 1% PVP K30 show the promising faster disintegration time (19.66 seconds) followed by rapid and highest drug release (95.80%) within 120 seconds. How to cite this article: Thakur, S., Sethi, V.A., Siddiqui, A.W. and Tyagi, L.K. (2019). Development of Mouth Dissolving Films (MDFs) of Ondansetron Hydrochloride By Using Factorial Experimental Design. International Journal of Drug Delivery Technology, 9(4): 517-524.

Formulation and In-Vitro Evaluation of Darifenacin Hydrobromide as Buccal Films

Darifenacin hydrobromide (DH) is the more recent uroselective M3 receptor antagonist for treating uncomplicated overactive bladder (OAB). This study was aimed to formulate DH as fast dissolving buccal films (FDBFs) using a solvent casting method to enhance patient’s compliance.
 Films were prepared by using polyvinyl alcohol (PVA) as a film forming polymer. Different types and concentrations of superdisintegrants (croscarmellose sodium, sodium starch glycolate, indion 414) were used to select the best formula by studying the physicochemical properties of the films, disintegration time (DT) and percent drug release.
 The results revealed that formula (F9) that containing 7.5mg DH, 2%w/v PVA, 30%w/w glycerol, 0.5%w/v tween 80, 4%w/w indion 414 was the preferred formula. F9 showed the shortest in-vitro disintegration time (31.28sec). In-vitro dissolution profile showed the lowest T80% of the drug in 3.05 min and the highest release of the drug (94%) within 5 min (D5min %).
 It was concluded that the FDBFs of DH could be considered as a promising drug delivery system with an enhanced disintegration and dissolution rate and better patient compliance.

Formulation and Evaluation of Cyclodextrin-Based Thermosensitive In Situ Gel of Azithromycin for Periodontal Delivery

This study aims to formulate and evaluate the temperature-sensitive in situ gel of 0.5% (w/v) azithromycin (AZM) containing cyclodextrin inclusion complex by the cold method. To increase its aqueous solubility, it was incorporated as an inclusion complex in a 1:1 M ratio with hydroxypropyl β-cyclodextrin (HPβ-CD). The central composite design was used to optimize the effect of poloxamer 407 and Carbopol 934P (independent factors) on dependent factors such as percentage drug release at first hour (t50% and t90%), gelation temperature, and viscosity. Both the independent factors had a significant effect on the entire five response factors (p < 0.05). Each formulation was evaluated for clarity, pH, spreadability, syringeability, gelation strength, mucoadhesive property, in vitro drug release, gelation temperature, viscosity, and rheology. Based on maximum desirability, formulation containing 18.91% (w/v) of poloxamer 407 and 0.353% (w/v) of Carbopol 934P was considered an optimized batch. The value of percentage relative error exhibited a close agreement between observed and predicted values calculated using regression equations. Further, the optimized formulation showed a good drug release for a period of 54 h, which was more effective in the treatment of periodontal disease. Thus, azithromycin (AZM) can be successfully formulated as a thermosensitive in situ mucoadhesive gel containing HPβ-CD for periodontal drug delivery.

Formulation and evaluation of the topical ethosomal gel of melatonin to prevent UV radiation.

Clinically, melatonin (MLT) has variable oral absorption and extensive first-pass effect, making its oral mode less preferable. Ethosomes are able to permeate intact through the human skin due to its high deformability. Present study assessed topical potential of ethosomes loaded with MLT for the prevention of UV radiation. Melatonin was encapsulated using different ratios of ethanol, soya lecithin, and cholesterol. Prepared ethosomes were characterized for scanning electron microscopy (SEM), zeta potential, % entrapment efficiency (%EE), in vitro drug release kinetics. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, in vitro skin permeation study, flux, and stability. Ethosomes were spherical in structure as confirmed by SEM, and zeta potential was in range of -12.4mV to -27.4mV. %EE of the vesicles was in the range of 49.61%-78.047%. Cumulative percentage drug release from various ethosomal formulations was ranged from 64.82%-81.01%. F3 was selected as optimized formulation on the basis of highest %EE, zeta potential, and in vitro drug release. An ethosomal gel of optimized formulation F3 was prepared by using carbopol 934 and compared with plain gel formulation. G3 formulation showed pseudoplastic rheological behavior, optimum pH, spreadability and also showed maximum % in vitro drug permeation with flux 13.85μg/cm2 /hr and followed zero-order release kinetics which was good for topical drug delivery system. This research suggested that MLT loaded ethosomes can be potentially used as a topically drug delivery system.

FORMULATION AND IN-VITRO EVALUATION OF THEOPHYLLINE HYDROCHLORIDE EFFERVESCENT FLOATING TABLETS: EFFECT OF POLYMER CONCENTRATION ON TABLET BUOYANCY

Objective: This study was undertaken to formulate a floating drug delivery system of theophylline hydrochloride using different concentrations of a chosen polymer and then investigate how polymer concentration affects buoyancy and drug release properties of the tablets.&#x0D; Methods: Hydroxypropyl methylcellulose (HPMC) at different concentration levels of 15% (F1), 20% (F2) and 30% (F3) was used to form the three formulation batches of floating tablets. Wet granulation method was used for the granule preparation while Sodium bicarbonate and citric acid were used as the gas generating agent. The physical properties of the granules and the floating tablets were evaluated. Also determined were the physicomechanical properties, buoyancy and swelling characteristics of the tablets. The in vitro drug release study was carried out according to the USP I (basket method) for 8h in 900 ml 0.1N HCl at 50 rpm. Samples withdrawn at the regular predetermined time were analyzed spectrophotometrically at a wavelength of 271 nm and data obtained statistically analyzed by one-way analysis of variance (ANOVA). The differences between means were considered significant at P&lt;0.05.&#x0D; Results: The result showed that polymer (HPMC) concentration significantly (p&gt;0.05) increased swelling index and improved floating lag time, it had no significant effect on the total floating time. Percentage drug release at the end of 8 h was 100%, 98.2% and 96.13% for formulation F1, F2 and F3, respectively. All three formulations followed the Higuchi drug release kinetics model and the mechanism of drug release was the non Fickian diffusion with exponents of 0.46, 0.51 and 0.56 for the respective batch.&#x0D; Conclusion: Batch F3 gave a better-controlled drug release and floating properties in comparison to batch F1 and F2 thus Polymer concentration influenced the onset of floating and controlled the release of Theophylline.

Design and in vivo Evaluation of Manidipine by Self-Nanoemulsifying Drug Delivery Systems

The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml and 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.

IMPLEMENTATION OF QUALITY BY DESIGN (QBD) APPROACH IN FORMULATION AND DEVELOPMENT OF RITONAVIR PELLETS USING EXTRUSION SPHERONIZATION METHOD

Objective: Ritonavir is an antiretroviral drug used for HIV-AIDS treatment. The purpose of this research work was to implement the quality by design (QbD) approach in formulation of ritonavir sustained-release pellets by industrially applied extrusion spheronization technique.&#x0D; Methods: Pellets were prepared by extrusion spheronization method and evaluated for their physicochemical properties. Initially, on the basis of prior knowledge Quality Target Product Profile (QTTP) element was identified and further Critical Quality Attributes (CQA) elements were defined. Risk assessment (RA) was done by two tools as failure mode and effect analysis (FMEA) and fishbone diagram (Ishikawa plot). Placket Burman design was implemented as a screening design using seven high-risk factors (spheronization speed, spheronization time, extrusion speed, drying method, PVP K 30, cross povidone, and solvent). Optimization study was done by 23 full factorial design with three critical factors as (spheronization speed, extrusion speed and PVP K 30). The in vitro drug release was studied in both gastric and intestinal fluids for 12 h using USP Ι apparatus. Control space was established for the sustained release pellets.&#x0D; Results: Among all batches obtained in 23 full factorial design, batch R7 was found to be effective with carr’s index value of 5.281, percentage yield of 69.6%, time required to release 50% drug was 8 h and percent drug release after 12 h was found 83.132 %, R7 batch was selected as optimized batch. Statistical analysis showed model terms were significant.&#x0D; Conclusion: We can conclude that; sustained-release pellets of ritonavir were successfully designed using QbD approach.