DEVELOPMENT OF ZOLMITRIPTAN MOUTH DISSOLVING FILMS: FORMULATION VARIABLES, MECHANICAL PROPERTIES, AND IN VITRO DRUG RELEASE STUDIES

Objective: The objective of the present investigation is to prepare zolmitriptan (ZOL) mouth dissolving films (MDFs) and to investigate the influence of formulation variables on physicomechanical, chemical, and drug release properties of the prepared MDFs. Methods: The MDFs were prepared by solvent casting technique using wet film applicator. The impact of hydroxypropyl methylcellulose of different viscosity grades (hydroxy propyl methyl cellulose [HPMC] E3, E5, and E15), plasticizers (glycerol and polyethylene glycol [PEG]-400), and solubilizing agents (polyvinyl pyrrolidone [PVP K30] and sodium lauryl sulfate [SLS]) on physicomechanical, chemical, and drug release properties were evaluated. The MDFs were also characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry studies. Results: The MDFs prepared were transparent and smooth and showed no recrystallization. The tensile strength of the MDFs increased significantly with an increase in polymer viscosities, and about a 2.63-fold increase in tensile strength was observed for HPMC E15 MDFs compared to E3, whereas an increase in film thickness resulted in brittle MDFs with low tensile strength. Similar results were observed with percent elongation and folding endurance of the MDFs. In vitro, drug release studies indicate that higher film thickness and polymer viscosities delayed the MDF disintegration and, in turn, the ZOL release. Addition of PVP K30 and SLS to HPMC E3 formulations resulted in 1.66- and 1.53-fold increase in ZOL release rates. Conclusion: Overall, F7 formulation showed quicker disintegration (within 11 s) and ZOL release rates (within 180 s) along with good physicomechanical properties. These results indicated that the disintegration and drug release of ZOL can be enhanced to a greater extent by optimizing formulation variables in MDFs

Development of Capecitabine Floating Tablet Dosage Forms for Treating Stomach Cancer

Objective: In the present research work, oral gastro retentive dosage forms (GRDFs) of capecitabine (CPC) were formulated using floating concept. Methods: GRDFs were formulated using hydroxypropyl methyl cellulose (HPMC K4M and K15M) as drug release retardant, sodium bicarbonate (NaHCO3) and calcium carbonate (CaCO3) as gas generating agents, and micro crystalline cellulose (MCC), dicalcium phosphate (DCP), spray dried lactose (SDL), and pre gelatinized starch (PGS) as fillers. The tablets were prepared by direct compression method and evaluated for various parameters. The GRDFs were also characterized by Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Results and Discussion: All the formulations were subjected for pre and post compression parameters, shows all the data within the limits. The lag times of GRDFs has decreased significantly for formulations containing calcium carbonate when compared to sodium bicarbonate as gas generating agent. In vitro drug release studies indicate that higher polymer concentration delayed the CPC release, and the sustaining effect was in the order K4M > K15M > LVCR 100. Addition of MCC, DCP, SDL, and PGS as fillers further affected the lag time and in turn the CPC release rates. Conclusion: The formulation (F9) containing 10%w/w HPMC K4M as the release retardant, microcrystalline cellulose as filler and 20%w/w CaCO3 as gas generating agent fulfilled regulatory requirements in terms of percent drug release at the end of 24h. Keywords: Capecitabine, Gastro retentive floating tablets, floating drug delivery systems, FTIR, DSC

Characterization and Estimation of Harpagoside in Dried Root Extract and Oral Powder Formulations of Harpagophytum Procumbens by Validated RP-HPLC-PDA Method

The present investigation was undertaken to perform structural, physicochemical characterization and to estimate the harpagoside in dried root extract and flavoured powder formulations of harpagophytum procumbens (devils claw). The extraction of harpagoside from the root extract was carried out using different solvents and the harpagoside content was estimated using an RP-HPLC-PDA method. The HPLC analysis was carried out using methanol: 0.02% formic acid (60:40 v/v) as the mobile phase, pumped at flow rate of 1mL/min through C18 column (Kinetex XB, 150x4.6mm, 5µ). The structural and physicochemical characterization of the root extract was performed using FT-IR, DSC and SEM analysis. Flavoured powder formulations (effervescent and non-effervescent) of the root extract were prepared and the harpagoside content was estimated by HPLC method. Higher percentage of harpagoside (1.6 %) was extracted with water as extraction solvent when compared to methanol and methanol: water (50:50 v/v). The developed RP-HPLC-PDA method resulted in shorter elution time (harpagoside was eluted at 5.3min) and the method was linear with good regression coefficient (R2>0.998) within the concentration range tested (0.2-4µg/mL). The FT-IR spectra of root extract showed the presence of characteristic peaks corresponding to the harpagoside and the results from photomicrographs and SEM analysis revealed spherical morphology of the particles in the extract. The prepared powdered formulations readily dispersed and dissolved in water and showed more than 98% of harpagoside content even after 6months time period indicating the stability of the formulations. Overall, the results from the present investigation can form basis to establish standardization parameters for formulations containing root extract of devil’s claw. Keywords: Harpagophytum procumbens, Structural and physicochemical characterization, RP-HPLC-PDA method, FT-IR, DSC, SEM

Development and Validation of RP-HPLC-PDA Method for the Analysis of Diclofenac Sodium in the In Vitro Transdermal Permeation Samples

A new analytical method using high-performance liquid chromatography coupled with photo diode array detection was developed and validated for the quantification of Diclofenac (DIC) from in vitro skin permeation samples. Analysis was performed using a Phenomenex C18 column (150 x 4.6mm, 5µm) with 10mM ammonium acetate: Acetonitrile (62:38% v/v) as the mobile phase in isocratic mode and eluents were monitored at 276nm. DIC was eluted at 3.1min and showed a good linearity in the concentration range of 0.2-3µg/mL with a correlation coefficient >0.999. The validation parameters, such as specificity, linearity, accuracy and limit of detection, limit of quantification, precision, robustness fulfilled the regulatory requirements. The developed HPLC method was successfully used for the analysis of DIC in samples obtained from transdermal diffusate samples

FORMULATION AND EVALUATION OF RAMIPRIL MOUTH DISSOLVING FILMS

Objective: The present investigation was aimed at preparation and evaluation of mouth dissolving films (MDFs) of Ramipril to enhance patient convenience, compliance and to improve bioavailability. Methods: MDFs with 0.5% w/w Ramipril were prepared by a solvent casting method using a wet film applicator. The effects of film formers, wetting/solubilizing, saliva stimulating agents and film modifiers on the physicomechanical and in vitro Ramipril release from MDFs were evaluated. Results: The MDFs prepared were transparent, smooth and showed no re-crystallization upon storage. MDFs casted with hydroxypropyl methylcellulose (HPMC) E3 as film former and polyethylene glycol (PEG-400) as plasticizer showed superior Ramipril release rates and good physicomechanical properties when compared to MDFs with E5 and E15 as film formers. HPMC E3 MDFs with polyvinyl pyrrolidone K30 (PVP K30) and sodium lauryl sulphate (SLS) gave superior drug release properties than MDFs without PVP K30 and SLS. The HPMC E3 MDFs with citric acid (CA) as saliva stimulating and xylitol as soothing agent gave significantly superior in vitro drug release than the MDFs without CA and xylitol. Release kinetics data reveals diffusion as a drug release mechanism. Conclusion: From the obtained results, it can be concluded that the administration of Ramipril as MDF may provide a quick onset of action with enhanced oral bioavailability and therapeutic efficacy

Formulation and Evaluation of Chlorpheniramine Maleate Mouth Dissolving Films

The present investigation was aimed at preparation and evaluation of mouth dissolving films (MDFs) of an anti-histamine drug, Chlorpheniramine Maleate (CPM) to enhance convenience and compliance to the elderly and paediatric patients. The MDFs were prepared using wet film applicator and evaluated for physicochemical and physicomechanical properties. MDFs were prepared with 0.6% and 0.8% w/w CPM. The MDFs with 0.8% w/w drug load showed re-crystallisation within 10 days, while the MDFs with 0.6% w/w CPM load were transparent with no re-crystallization. The effect of film formers, film thickness, film modifiers, saliva stimulating and soothing agents on the physicomechanical properties and CPM release from MDFs were evaluated. MDFs casted at 30mil thickness containing poly ethylene glycol (PEG-400) as plasticizer showed superior CPM release rates along with good physicomechanical properties. MDFs with hydroxy propyl methyl cellulose (HPMC) E3 as film former gave superior CPM release rate when compared to E5 and E15 formulations. MDFs with poly vinyl pyrrolidone K30 (PVPK30) gave superior drug release properties when compared to MDFs without PVP K30. The MDFs with citric acid (CA) and xylitol gave superior CPM release than the other MDFs. Release kinetics data reveals diffusion as drug release mechanism

Lidocaine-loaded fish scale-nanocellulose biopolymer composite microneedles

Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture

Microneedle assisted transdermal delivery of zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

Objective: The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). Methods: Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77cm2 skin area (PM-3) to maintain the MN density closer to 0.6mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Results: Micro-injection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17 and 3.65 fold increase in ZMT flux values were observed with 1.5mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. Discussion: Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. Conclusion: The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

Application of microneedle arrays for enhancement of transdermal permeation of Insulin: in vitro experiments, scaling analyses and numerical simulations

The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses was done using dimensionless parameters like concentration of drug (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN treated skin and experimental parameters like passive diffusion coefficient. A 1.6 fold increase in transdermal flux and 1.9 fold decrease in lag time values were observed with 1.5mm MN when compared with passive studies. Good correlation (R2>0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f2≥50). Insulin permeation significantly increased with increase in donor concentration and MN length (p<0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans

Effect of microneedle type on transdermal permeation of rizatriptan

The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (Ct/Cs), thickness (h/L) and surface area (Sa/L2) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement