PREPARATION AND EVALUATION OF RAPIDLY DISSOLVING TABLETS OF RALOXIFENE HYDROCHLORIDE BY TERNARY SYSTEM FORMATION

Objectives: Enhancing the dissolution rate of raloxifene hydrochloride for the preparation of rapidly disintegrating tablets with subsequent rapid dissolution.Methods: Binary and ternary solid dispersions (SDs) with different carriers were prepared at various drug: carrier ratios including cremophor RH 40, polyvinylpyrrolidone (PVP K30), poloxamer 407 and gelucire 44/14 as carriers and were evaluated by drug content, In-vitro dissolution studies, Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analysis analysis. The most efficient solid dispersion was selected for preparation of rapidly dissolving tablets.Results: SDs showed enhanced dissolution rate compared to the unprocessed drug. Differential scanning calorimetry revealed that enhancement in drug dissolution was mainly due to a change in its crystalline structure. FTIR studies revealed no interaction between the drug and excipients. The dissolution pattern of the drug from the prepared tablet depended on the components of the tablets with those containing a combination of super-disintegrants (crospovidone and croscarmellose) in the presence of citric acid as channeling agent and pH modifier being the best.Conclusion: The study presented a system capable of increasing the dissolution rate of raloxifene with successful incorporation in rapidly disintegrating tablets with subsequent fast dissolution. 3

Penetration enhancers in proniosomes as a new strategy for enhanced transdermal drug delivery

AbstractThe aim of this work is to investigate penetration enhancers in proniosomes as a transdermal delivery system for nisoldipine. This was performed with the goal of optimising the composition of proniosomes as transdermal drug delivery systems. Plain proniosomes comprising sorbitan monostearate, cholesterol, ethanol and a small quantity of water were initially prepared. Subsequently, proniosomes containing lecithin or skin penetration enhancers were prepared and evaluated for transdermal delivery of nisoldipine. The plain proniosomes significantly enhanced the transdermal flux of nisoldipine to reach 12.18μgcm−2h−1 compared with a saturated aqueous drug solution which delivered the drug at a rate of 0.46μgcm−2h−1. Incorporation of lecithin into such proniosomes increased the drug flux to reach a value of 28.51μgcm−2h−1. This increase can be attributed to the penetration enhancing effect of lecithin fatty acid components. Replacing lecithin oleic acid (OA) produced proniosomes of comparable efficacy to the lecithin containing system. The transdermal drug flux increased further after incorporation of propylene glycol into the OA based proniosomes. Similarly, incorporation of isopropyl myristate into plain proniosomes increased drug flux. The study introduced enhanced proniosomes as a promising transdermal delivery carrier and highlighted the role of penetration enhancing mechanisms in enhanced proniosomal skin delivery. The study opened the way for another line of optimisation of niosome proconcentrates

INTESTINAL ABSORPTION OF EPROSARTAN MESYLATE FROM SELF EMULSIFYING SYSTEM AND CYCLODEXTRIN COMPLEX

Objective: The aim of this work was to determine the intestinal membrane transport parameters of eprosartan mesylate (EM) and to investigate self-nano emulsifying drug delivery systems (SNEDDS) and inclusion complexation with hydroxypropyl b cyclodextrin (HPbCD) for enhanced intestinal absorption of eprosartan mesylate. Methods: The intestinal absorption was monitored using the in situ rabbit intestinal perfusion technique. SNEDDS was developed using labrafil, Lauroglycol with a tween in the presence of ethanol. Inclusion complexation was achieved by construction of phase solubility diagram in the presence of HPbCD. The prepared complex was evaluated using Fourier Transform Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The drug was found to be poorly absorbed from the jejuno-ileum and the colon with the absorption being mainly through paracellular pathway. An inclusion complex was developed between the drug and HPβCD. Perfusion of the drug in the nanoemulsion formulation or as an inclusion complex resulted in a significant increase in the intestinal absorption of the drug compared with the control.Conclusion: SNEDDS and inclusion complexation are promising strategies for enhanced intestinal absorption of eprosartan mesylate

Efficacy and Safety of Topical Tranexamic Acid Alone or in Combination with Either Fractional Carbon Dioxide Laser or Microneedling for the Treatment of Melasma

Introduction: Tranexamic acid (TXA) is a promising treatment modality for melasma. Microneedling (MN) and fractional carbon dioxide (CO2) laser were reported to enhance TXA transepidermal delivery. Objectives: To compare efficacy and safety of topical TXA alone or in combination with either fractional CO2 laser or MN for treatment of melasma. Methods: Thirty females with facial melasma were divided randomly into 3 equal groups after excluding pregnant and lactating women and those using oral contraceptives or other hormonal therapy. Patients of group A were treated with fractional CO2 laser and those of group B were treated with MN (4 sessions, 3 weeks apart for both) with immediate topical application of TXA 5% solution after sessions and daily application of 5% TXA cream for both groups. Patients of group C were treated by topical daily application of TXA 5% cream. Evaluation was done by modified melasma area and severity index scores (mMASI), patient satisfaction and dermoscopy. Results: Statistically significant improvement of mMASI was reported in all studied groups with a significantly better improvement in patients of groups A and B than those of group C, meanwhile the difference between groups A and B was statistically insignificant. Conclusions: Topical TXA is a safe and fairly effective treatment modality for facial melasma. Combining TXA with either fractional CO2 laser or MN yielded significantly better improvement than when used alone. Fractional CO2 laser carries the risk of post-inflammatory hyperpigmentation in patients with skin types III and IV and requires meticulous patient selection

Topical Oxybutynin 3% Gel versus Aluminum Chloride 15% Lotion in Treatment of Primary Focal Hyperhidrosis

Introduction: Hyperhidrosis is excessive sweating beyond thermoregulatory needs. It is a potentially disabling condition with challenging management. Aluminum chloride is the established topical treatment; however, response remains unsatisfactory. Oxybutynin is an anticholinergic drug that stands as a therapeutic chance for hyperhidrosis. Objectives: comparing the efficacy of topical oxybutynin 3% gel versus aluminum chloride 15% lotion in treatment of primary focal hyperhidrosis. Methods: Forty patients with hyperhidrosis were randomly distributed into 2 equal groups treated by either topical oxybutynin 3% gel or topical aluminum chloride 15% lotion once daily night application for 4 weeks (both groups). Evaluation was done at 2 and 4 weeks of treatment and after 1 month of the end of treatment for follow up by Minor iodine starch test, hyperhidrosis disease severity scale (HDSS) and dermatology life quality index (DLQI). Results: Both treatment modalities were effective with insignificant differences between patients of both groups regarding improvement in Minor iodine starch test and HDSS after 2 weeks of treatment (P = 0.561, 0.33 respectively). Oxybutynin 3% gel yielded significantly better improvement of Minor’s test, HDSS and patient’s quality of life at the end of 4 weeks of treatment with lower recurrence rate than aluminum chloride 15% lotion at 1 month follow up. Minimal adverse effects were noted in both studied groups. Conclusions: Oxybutynin 3% gel could be considered as a promising treatment modality for hyperhidrosis with higher efficacy than aluminum chloride 15% lotion and lower recurrence rate

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gel

Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

Alginate vehicles are capable of forming gel matrix in situ, when comes into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethrophan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a sustained release commercial liquid which is based on ion exchange resin. The release pattern indicated strict control of drug release both in the gastric and intestinal conditions, suggesting the potential advantage of using solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependant alginate gels

Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine

Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth), propylene glycol (PG), polyethylene glycol 400 (PEG), and oleic acid (OA) and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6 mg/ml) and flux (40.8 μg/cm2 h) was achieved by Eth and the lowest piperine flux (1.17 μg/cm2 h) was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25) binary system had the highest piperine flux (59.3 μg/cm2 h) followed by Eth-OA (50:50) (32.3 μg/cm2 h) and PG-OA (90:10) (22.7 μg/cm2 h). The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine