Pulsatile Delivery of Fexofenadine Hydrochloride Pulsincap by Box-Behnken Design

Objective: Fexofenadine hydrochloride is a selective peripheral H1-blocker, used for allergy symptoms, such as hay fever and urticaria. Allergic symptoms are aggressive during early morning hours, so a pulsatile delivery system with a lag time of 4-5 hours was formulated and optimized by Box-Behnken design. Materials and Methods: Pulsincap system using formaldehyde-treated capsules and hydrogel plug. Box-Behnken design was applied for optimization in which three independent variables, X1= Drug: polymer ratio, X2 = Polymer: polymer ratio (Ethylcellulose: HPMC E15) and X3 = Plug weight were selected. Three dependent variables R1 = Percent release of drug after 4 hours, R2 = percent release after 10 hours and R3 = Lag time were selected. Results: FTIR and DSC studies confirmed compatibility of drug and excipients. The empty formaldehyde-treated capsules were evaluated for physical appearance, solubility, capsule dimensions and formaldehyde content. Hydrogel plugs, powder blend and pulsincap formulations were evaluated for Physico-chemical parameters and all the parameters were within acceptable limits. Contour plots and Response surface plots indicated that as Drug: Polymer ratio (X1) and Plug weight (X3) increased, Lag time increased but% drug release decreased. As Polymer: Polymer ratio (X2) increased, the lag time was at a moderate level. Predicted vs actual responses showed the correlation of 0.786 for% release in 4hrs, 0.9744 for% release in 10hrs and 0.6281 for lag time. Optimized formulation G1 was suggested by design (with criteria 4.5-6hrs lag time, 10-20% release in 4hrs & 60-70% drug release within 10hrs). The optimised formulation was stable. Conclusion: Pulsincap system of Fexofenadine hydrochloride can be obtained by using retarding polymers like ethyl cellulose, HPMC E15 and formaldehyde cross-linked capsules.

Fabrication and Evaluation of Mouth Dissolving Strips of Metoclopramide Hydrochloride by Using Novel Film Former

Fast dissolving strips are used as novel approaches, as it dissolves rapidly in mouth and directly reaches the systemic circulation. In present research work, an attempt has been made to prepare mouth dissolving strips of Metoclopramide hydrochloride by using a novel film former Pullulan by solvent casting method. A33 full factorial design was utilized for the optimization of the effect of independent variables such as the amount of Pullulan, amount of PEF 400, amount of SSG on mechanical properties, and % drug release of strips. The drug compatibility studies using FTIR and DSC studies formulated strips were characterized for their physicochemical parameter like weight variation, visual appearance, folding endurance, thickness, disintegration time, drug content, and in vitro dissolution studies. FTIR and DSC studies revealed that the polymer is compatible with the drug. It was found that the optimum levels of the responses for a fast release strip could be obtained at low levels of Pullulan, PEG400, and SSG. The prepared strip was clear transparent and had a smooth surface. The surface pH was found 4.8 to 5.2 be in the range of to which is close to salivary pH, which indicates that strips may have less potential to irritate the oral mucosa, thereby they are comfortable. The drug release was found to be between 90.94 to 100.5% in 2 min. The in-vitro disintegration time of strips prepared with Pullulan was in the range of 19 to 57 sec. As the concentration of SSG increases the decrease in the disintegration time of strips a decrease. The dissolution rate increased with an increase in the concentration of SSG. Hence, it can be inferred that the fast dissolving oral strips of Metoclopramide hydrochloride may produce rapid action thereby improving bioavailability and enhance the absorption by avoiding the first-pass effect.

Formulation and Evaluation of Atorvastatin Solid Dispersions using Entada scandens seed starch as Superdisintegrant

The present work mainly focuses on solubility enhancement of poorly soluble drugs using superdisintegrants. One of such poorly soluble drugs is Atorvastatin, which belongs to the category of statins. Atorvastatin belongs to BCS class – II, which is poorly water soluble and highly permeable. Natural sources are now-a-days playing a key role in pharmaceutical research. They have several pharmaceutical applications. Starches obtained from plants are pharmaceutically useful as binders, diluents, disintegrants and lubricants. Various physical parameters were evaluated. Solid dispersions were prepared using solvent evaporation technique. Where as in solid dispersions, formulations F2 and F5 showed better dissolution rate compared with other formulations. Fourier Transform Infra red spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies for optimized formulations revealed that there were no major interactions between the drug and excipients. X-Ray Diffraction (XRD) studies revealed the crystalline and amorphous nature of formulations. Scanning Electron Microscopy (SEM) revealed the surface characteristics. Thus from the present study, it was concluded that Entada scandens seed starch posses superdisintegrant property.

Properties of Mosquito Repellent-Plasticized Poly(lactic acid) Strands

Poly(lactic acid) (PLA) is an attractive candidate for replacing petrochemical polymers because it is fully biodegradable. This study investigated the potential of PLA as a sustainable and environmentally friendly alternative material that can be developed into commercially viable wearable mosquito repellent devices with desirable characteristics. PLA strands containing DEET and IR3535 were prepared by twin screw extrusion compounding and simultaneously functioned as plasticizers for the polymer. The plasticizing effect was investigated by thermal and rheological studies. DSC studies showed that the addition of DEET and IR3535 into PLA strands reduced the glass transition temperature consistent with predictions of the Fox equation, thus proving their efficiency as plasticizers. The rheology of molten samples of neat PLA and PLA/repellents blends, evaluated at 200 °C, was consistent with shear-thinning pseudoplastic behaviour. Raman studies revealed a nonlinear concentration gradient for DEET in the PLA strand, indicating non-Fickian Type II transport controlling the desorption process. Release data obtained at 50 °C showed initial rapid release followed by a slower, near constant rate at longer times. The release rate data were fitted to a novel modification of the Peppas-Sahlin desorption model.

Mouth Dissolving Film of Domperidone: An approach towards Formulation and its Evaluation

The objective of the current work is to formulate and evaluate the mouth dissolving film of domperidone. It is ideally suitable for the treatment of emesis. The mouth dissolving film of domperidone is useful in the vomiting through the journey. Mouth dissolving films were formulated by the solvent casting technique and its in-vitro as well as the in-vivo evaluation was done by the usual pharmacopoeial and unofficial tests and by using human volunteers. The main benefit of the preparation technique includes fewer operation units, better content consistency. The mouth dissolving film formed was found to be disintegrated in 1 minute. The ratio of components in the aqueous phase affected the thickness, drug content, tensile strength, percentage elongation, folding endurance, and release profile of mouth dissolving film and the best results were obtained for the HPMC E15 and polyethyleneglycol. The compatibility between domperidone and excipients was confirmed by FTIR and DSC studies. The developed mouth dissolving film of domperidone demonstrated usefulness for fast release of drug in mouth, for better drug utilization, and improved patient compliance. The optimized formulation, due to low HPMC E15 content, has optimum tensile strength and thickness. Formulation F8 containing HPMC E15 and PG showed a cumulative % drug release of 95.10 at the end of 12 minutes. HPMC E15 films showed higher cumulative % drug release than films of other HPMC E grades at different concentrations. It was found to be stable during the accelerated stability study. The effect of different concentrations of polymers and plasticizers on in-vitro evaluation parameters was evaluated. Hence, data showed that formulation F8 was the most suitable for the development of fast dissolving oral films of domperidone.

ROLE OF FUNCTIONALIZED GUAR GUM IN SOLID DISPERSION OF NON-STEOIDAL ANTI-INFLAMMATORY DRUG

The current investigation was developed to study the role of functionalized guar gum as carrier in solid dispersion of iboprofen. The solid dispersion technique using aminated guar gum would be an effective approach for increasing the solubility and increasing dissolution behaviour of ill fathomable medicament than the native guar gum. The results of FTIR and DSC studies confirmed that there is no chemical interaction or no incompatability between the drug and excipients. The invitro dissolution study was performed for the the prepared formulations. Based on the results SD3 was shown highest drug release 99.41% within 24hrs. Stabiliy study was conducted as per ICH guidelines and the falloutsrevealed that there is no physical or chemical change.it may be concluded that solubility of ibuprofen can br improved by using functionalized guar gum in the solid dispersion, which provides a wide scope for the therapeutic efficiency.

Design expert as a statistical tool for optimization of 5-ASA-loaded biopolymer-based nanoparticles using Box Behnken factorial design

Background The overall objective was to prepare a highly accurate nanocarrier system of mesalamine for the treatment of ulcerative colitis with increased therapeutic efficacy and targeting. In the formulation of nanocarrier systems, optimization is a critical process for understanding nanoformulation variables and quality aspects. The goal of the present work was to determine the effect of independent variables, i.e., the concentrations of chitosan, carboxymethyl inulin (CMI), and the drug on the response variables, i.e., particle size and percent entrapment efficiency of the mesalamine-loaded nanoparticle using the Box Behnken design (BBD). The correlation between the independent and dependent variables was investigated using the Design Expert generated mathematical equations, contour, and response surface designs. Result An optimized batch was developed using the ionotropic gel method with selected independent variables (A: + 1 level, B: 0 level, C: − 1 level) and the developed nanoparticles had a particle size of 184.18 nm, zeta potential 26.54 mV, and entrapment efficiency 88.58%. The observed responses were remarkably similar to the predicted values. The morphological studies revealed that the formulated nanoparticles were spherical, and the results of the FTIR and DSC studies indicated the drug-polymer compatibility. The nanoparticle showed less than 5% release in the pH 1.2. In the colonic region (pH 7.4), more than 80 % of the medication was released after 24 h. The kinetics study showed that the Higuchi and Korsemeyer-Peppas models had R2 values of 0.9426 and 0.9784 respectively, for the developed formulation indicating linearity, as revealed by the plots. This result justified the sustained release behavior of the formulation. Conclusion The mesalamine-loaded chitosan-CMI nanoparticle has been successfully developed using the ionotropic gelation method. The nanoparticles developed in this study were proposed to deliver the drug to its desired site. The developed nanoparticles were likely to have a small particle size with positive zeta potential and high percent drug entrapment. It could be stated from the results that BBD can be an active way for optimizing the formulation and that nanoparticles can be a potential carrier for delivering therapeutics to the colon.

Design and development of zolmitriptan niosomal in situ nasal gel for the treatment of migrain

The objective of the present study was to development of Zolmitriptan (ZMT) niosomal in situ nasal gel formulation for migraine treatment. By intranasal route delivered drug to the central nervous system (CNS) through the olfactory lobes, which bypasses the first-pass metabolism and consequently enhances the bioavailability. Noisome of ZMT were prepared by using the lipid film hydration method. Optimized niosomal formulation was used to prepare in situ gel. The developed Noisomal formulations were characterized for vesicle size, shape, zeta potential, entrapment efficiency, drug content and in-vitro diffusion study, mucoadhesive strength, permeation study, FTIR, DSC and XRD studies. The FTIR and DSC studies predicted that there was no any interaction in drug and excipients. ZMT niosomes were showed particle size, Polydispersity index (PDI), Zeta potential, % entrapment efficiency and drug content, 149nm, 0.223, -28.9, 88.16±0.8 % and 96.23±1.2% respectively. In-vitro diffusion study of niosomes shows 96.23±0.7% at 8h. The permeation rate of in situ niosomes gel and the pure drug was about 98.56% and 79.46%, respectively. XRD & DSC studies were showed that reduce crystalinity in the formulations. The SEM images of niosomes were found spherical in shape to some extent showing particle size distribution. Thus, it can be concluded that developed ZMT niosomal in situ gel formulation can be considered as a promising system for which may reduce dose requirement, improve patient acceptability and efficient targeting drug delivery to the brain through the olfactory lobe for migraine treatment.

Formulation of Non-effervescent Floating Dosage Form of Metronidazole using Sintering and Sublimation Technique

The aim of this study was to formulate a novel non-effervescent floating dosage form of metronidazole using the sublimation and sintering technique. Granules were formulated using the wet granulation technique. Ammonium bicarbonate (30% w/w) was incorporated as the sublimating agent. The granules were characterized for micromeritic properties. Thereafter, the granules were compressed using a single punch tableting machine and the physicotechnical properties were evaluated. The metronidazole tablet was then sintered at 70oC for 12 h. All granules were free flowing and compressible. The metronidazole tablets had no floating lag time showing that tablets floated instantaneously. FTIR and DSC studies showed that metronidazole and the excipients used in the formulation were compatible. Azadirachta indica gum was used in the formulation of non-effervescent floating dosage form of metronidazole using sublimation and sintering technique which is beneficial in sustained release formulations. Dhaka Univ. J. Pharm. Sci. 20(1): 11-17, 2021 (June)

Formulation and Optimization of Zolmitriptan Orodispersible Tablets

Zolmitriptan is a selective 5-hydroxytryptamine receptor agonist reported for the acute migraine treatment, having poor water solubility leads to poor bioavailability. In the present study, attempt to improve the bioavailability of zolmitriptan with the help of PVP K-30 using the microwave irradiation method. The zolmitriptan and PVP K- 30 in 1:1 ratio was subjected to microwave irradiation for different times such as 60,80,100,120 seconds at 650 watts. Characterization of solid dispersion was done by drug content, XRD, FTIR, DSC. FTIR analysis demonstrated there are no compatibility issues. XRD studies prove that the solid dispersion was in amorphous form. DSC studies prove that solid dispersion was amorphous based on the intensity of peaks. The prepared dispersion was made into orodispersible tablets by direct compression. The optimization of these formulations was carried out by using 32 factorial designs on Design Expert 10.0 software. In order to examine the effect of independent variables Crospovidone (X1), croscarmellose sodium (X2), and combined effect of independent variables 32 factorial design was selected. In this design, two responses such as disintegration time and % drug release were evaluated, and experimental trials are performed for all 9 formulations. For all formulations, the precompression and post-compression parameters were studied. Based upon the model optimized formulation (C1 and C2) was obtained having the disintegration time (34.4±0.84 and 39.8±0.91) and %drug release (98.7±0.42 and 93.2±0.46) respectively. Keywords: Zolmitriptan, Solid dispersion, Microwave irradiation, Crospovidone, Croscarmellose sodium.