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An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

Singh I, Nair RS, Gan S, Cheong V, Morris A

Pharm Dev Technol, 2019 Apr;24(4):448-454.
PMID: 30084268 DOI: 10.1080/10837450.2018.1509347

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Emerging frontiers of deep eutectic solvents in drug discovery and drug delivery systems

Zainal-Abidin MH, Hayyan M, Ngoh GC, Wong WF, Looi CY

J Control Release, 2019 12 28;316:168-195.
PMID: 31669211 DOI: 10.1016/j.jconrel.2019.09.019

The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
A review of bacterial cellulose-based drug delivery systems: their biochemistry, current approaches and future prospects

Abeer MM, Mohd Amin MC, Martin C

J Pharm Pharmacol, 2014 Aug;66(8):1047-61.
PMID: 24628270 DOI: 10.1111/jphp.12234

The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Use of artificial neural networks to predict drug dissolution profiles and evaluation of network performance using similarity factor

Peh KK, Lim CP, Quek SS, Khoh KH

Pharm Res, 2000 Nov;17(11):1384-8.
PMID: 11205731

PURPOSE: To use artificial neural networks for predicting dissolution profiles of matrix-controlled release theophylline pellet preparation, and to evaluate the network performance by comparing the predicted dissolution profiles with those obtained from physical experiments using similarity factor.
METHODS: The Multi-Layered Perceptron (MLP) neural network was used to predict the dissolution profiles of theophylline pellets containing different ratios of microcrystalline cellulose (MCC) and glyceryl monostearate (GMS). The concepts of leave-one-out as well as a time-point by time-point estimation basis were used to predict the rate of drug release for each matrix ratio. All the data were used for training, except for one set which was selected to compare with the predicted output. The closeness between the predicted and the reference dissolution profiles was investigated using similarity factor (f2).
RESULTS: The f2 values were all above 60, indicating that the predicted dissolution profiles were closely similar to the dissolution profiles obtained from physical experiments.
CONCLUSION: The MLP network could be used as a model for predicting the dissolution profiles of matrix-controlled release theophylline pellet preparation in product development.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Design of a 24-hour controlled porosity osmotic pump system containing PVP: formulation variables

Yakubu R, Peh KK, Tan YT

Drug Dev Ind Pharm, 2009 Dec;35(12):1430-8.
PMID: 19929202 DOI: 10.3109/03639040902988566

The purpose of this study was to design a 24-hour controlled porosity osmotic pump system that utilizes polyvinyl pyrrolidone (PVP) as an osmotic-suspending/release retarding agent of drugs.

Matched MeSH terms: Chemistry, Pharmaceutical/methods*
Effect of storage temperature on the stability of spray dried bacteriophage powders

Leung SSY, Parumasivam T, Nguyen A, Gengenbach T, Carter EA, Carrigy NB, et al.

Eur J Pharm Biopharm, 2018 Jun;127:213-222.
PMID: 29486303 DOI: 10.1016/j.ejpb.2018.02.033

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106-107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Design and Evaluation of Microemulsion-Based Drug Delivery Systems for Biofilm-Based Infection in Burns

Biswas A, A JM, Lewis SA, Raja S, Paul A, Ghosal K, et al.

AAPS PharmSciTech, 2024 Sep 05;25(7):203.
PMID: 39237802 DOI: 10.1208/s12249-024-02909-4

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
How Important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review

Johari S, Johan MR, Khaligh NG

Curr Med Chem, 2024;31(27):4286-4311.
PMID: 38243980 DOI: 10.2174/0109298673260463231122074253

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/ intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti- bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Matched MeSH terms: Chemistry, Pharmaceutical*
Fulltext Transitioning from Pickering emulsions to Pickering emulsion hydrogels: A potential advancement in cosmeceuticals

Rajoo A, Siva SP, Sia CS, Chan ES, Tey BT, Low LE

Eur J Pharm Biopharm, 2024 Dec;205:114572.
PMID: 39486631 DOI: 10.1016/j.ejpb.2024.114572

Cosmeceuticals, focusing on enhancing skin health and appearance, heavily rely on emulsions as one of the common mediums. These emulsions pose a challenge due to their dependence on surfactants which are essential for stability but are causing concerns about environmental impact as well as evolving consumer preferences. This has led to research focused on Pickering emulsions (PEs), which are colloidal particle-based emulsion alternatives. Compared to conventional emulsions, PEs offer enhanced stability and functionality in addition to serving as a sustainable alternative but still pose challenges such as rheological control and requiring further improvement in long-term stability, whereby the limitations could be addressed through the introduction of a hydrogel network. In this review, we first highlight the strategies and considerations to optimize active ingredient (AI) absorption and penetration in a PE-based formulation. We then delve into a comprehensive overview of the potential of Pickering-based cosmeceutical emulsions including their attractive features, the various Pickering particles that can be employed, past studies and their limitations. Further, PE hydrogels (PEHs), which combines the features between PE and hydrogel as an innovative solution to address challenges posed by both conventional emulsions and PEs in the cosmeceutical industry is explored. Moreover, concerns related to toxicity and biocompatibility are critically examined, alongside considerations of scalability and commercial viability, providing a forward-looking perspective on potential future research directions centered on the application of PEHs in the cosmeceutical field.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Fulltext Ringing medicinal chemistry: The importance of 3-membered rings in drug discovery

Uthumange SS, Liew AJH, Chee XW, Yeong KY

Bioorg Med Chem, 2024 Dec 15;116:117980.
PMID: 39536361 DOI: 10.1016/j.bmc.2024.117980

Scaffold-based drug design has become increasingly prominent in the pharmaceutical field due to the systematic and effective approach through which it facilitates the development of novel drugs. The identification of key scaffolds provides medicinal chemists with a fundamental framework for subsequent research. With mounting evidence suggesting that increased aromaticity could impede the chances of developmental success for oral drug candidates, there is an imperative need for a more thorough exploration of alternative ring systems to mitigate attrition risks. The unique characteristics exhibited by three-membered rings have led to their application in medicinal chemistry. This review explores the use of cyclopropane-, aziridine-, thiirane-, and epoxide-containing compounds in drug discovery, focusing on their roles in approved medicines and drug candidates. Specifically, the importance of the three-membered ring systems in rending biological activity for each drug molecule was highlighted. The undeniable therapeutic value and intriguing features presented by these compounds suggest significant pharmacological potential, providing justification for their incorporation into the design of novel drug candidates.

Matched MeSH terms: Chemistry, Pharmaceutical*
Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate

Phang HC, Ng ZQ, Mohamad N, Chew YL, Balaraman A, Kee PE, et al.

Drug Dev Ind Pharm, 2024 Sep;50(9):810-826.
PMID: 39320267 DOI: 10.1080/03639045.2024.2409168

BACKGROUND: Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset.
OBJECTIVE: This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films.
METHODS: Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterization tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young's modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behavior, accelerated stability, X-ray diffraction (XRD), and palatability.
RESULTS: FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 s), high flexibility (folding endurance > 300 times) and lower Young's modulus (1.308 ± 0.214).
CONCLUSION: Oven drying method has been proven to be favorable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Application of cocoa butter for formulation of fast melt tablets containing memantine hydrochloride

Loke YH, Phang HC, Gobal G, Vijayaraj Kumar P, Kee PE, Widodo RT, et al.

Drug Dev Ind Pharm, 2024 Oct;50(10):845-855.
PMID: 39418138 DOI: 10.1080/03639045.2024.2417999

INTRODUCTION: Fast melt tablets (FMTs) provide a convenient dosage form that rapidly dissolves on the tongue without the need for water. Cocoa butter serves as a suitable matrix system for FMTs formulation, facilitating rapid disintegration at body temperature.
OBJECTIVES: This study aimed to formulate FMTs using cocoa butter as a base and investigate the effect of various disintegrants and superdisintegrants on their characteristics.
METHODS: Cocoa butter-based FMTs were prepared via the fusion molding technique. Different disintegrants and superdisintegrants were added at varying concentrations and subjected to characterization. The optimal formulation was selected and incorporated with 10 mg memantine hydrochloride.
RESULTS: The optimal FMT formulation consisted of 340 mg cocoa butter, 75 mg starch, and 75 mg crospovidone, exhibiting a hardness of 17.12 ± 0.31 N and a disintegration time of 32.67 ± 0.17 s. Furthermore, FMTs demonstrated a faster release profile compared to the commercially available product, Ebixa. SEM micrographs revealed homogenous blending of individual ingredients within the cocoa butter matrix and FT-IR analysis confirmed the chemical stability of memantine hydrochloride in the formulation. The dissolution profile of F17 suggested that the drug in FMTs released faster compared to Ebixia. Memantine hydrochloride achieved 98.07% of drug release in FMTs at 10 min. Moreover, the prepared FMTs exhibited stability for at least 6 months.
CONCLUSION: The successful development of cocoa butter-based FMTs containing memantine hydrochloride highlights the potential of cocoa butter as viable alternative matrix-forming material for FMTs production. This innovative formulation offers patients a convenient alternative for medication administration.

Matched MeSH terms: Chemistry, Pharmaceutical/methods
Characterization and solubility study of norfloxacin-polyethylene glycol, polyvinylpyrrolidone and carbopol 974p solid dispersions

Gorajana A, Kit WW, Dua K

Recent Pat Drug Deliv Formul, 2015;9(2):167-82.
PMID: 25714525

OBJECTIVE: Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion.
METHODS: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated.
RESULTS: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8.
CONCLUSION: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.

Matched MeSH terms: Chemistry, Pharmaceutical
Fulltext Optimization of natural lipstick formulation based on pitaya (Hylocereus polyrhizus) seed oil using D-optimal mixture experimental design

Kamairudin N, Gani SS, Masoumi HR, Hashim P

Molecules, 2014;19(10):16672-83.
PMID: 25325152 DOI: 10.3390/molecules191016672

The D-optimal mixture experimental design was employed to optimize the melting point of natural lipstick based on pitaya (Hylocereus polyrhizus) seed oil. The influence of the main lipstick components-pitaya seed oil (10%-25% w/w), virgin coconut oil (25%-45% w/w), beeswax (5%-25% w/w), candelilla wax (1%-5% w/w) and carnauba wax (1%-5% w/w)-were investigated with respect to the melting point properties of the lipstick formulation. The D-optimal mixture experimental design was applied to optimize the properties of lipstick by focusing on the melting point with respect to the above influencing components. The D-optimal mixture design analysis showed that the variation in the response (melting point) could be depicted as a quadratic function of the main components of the lipstick. The best combination of each significant factor determined by the D-optimal mixture design was established to be pitaya seed oil (25% w/w), virgin coconut oil (37% w/w), beeswax (17% w/w), candelilla wax (2% w/w) and carnauba wax (2% w/w). With respect to these factors, the 46.0 °C melting point property was observed experimentally, similar to the theoretical prediction of 46.5 °C. Carnauba wax is the most influential factor on this response (melting point) with its function being with respect to heat endurance. The quadratic polynomial model sufficiently fit the experimental data.

Matched MeSH terms: Chemistry, Pharmaceutical
Stability indicating HPLC-UV method for detection of curcumin in Curcuma longa extract and emulsion formulation

Syed HK, Liew KB, Loh GO, Peh KK

Food Chem, 2015 Mar 1;170:321-6.
PMID: 25306352 DOI: 10.1016/j.foodchem.2014.08.066

A stability-indicating HPLC-UV method for the determination of curcumin in Curcuma longa extract and emulsion was developed. The system suitability parameters, theoretical plates (N), tailing factor (T), capacity factor (K'), height equivalent of a theoretical plate (H) and resolution (Rs) were calculated. Stress degradation studies (acid, base, oxidation, heat and UV light) of curcumin were performed in emulsion. It was found that N>6500, T<1.1, K' was 2.68-3.75, HETP about 37 and Rs was 1.8. The method was linear from 2 to 200 μg/mL with a correlation coefficient of 0.9998. The intra-day precision and accuracy for curcumin were ⩽0.87% and ⩽2.0%, while the inter-day precision and accuracy values were ⩽2.1% and ⩽-1.92. Curcumin degraded in emulsion under acid, alkali and UV light. In conclusion, the stability-indicating method could be employed to determine curcumin in bulk and emulsions.

Matched MeSH terms: Chemistry, Pharmaceutical
Fulltext Nanoscale drug delivery systems and the blood-brain barrier

Alyautdin R, Khalin I, Nafeeza MI, Haron MH, Kuznetsov D

Int J Nanomedicine, 2014;9:795-811.
PMID: 24550672 DOI: 10.2147/IJN.S52236

The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.

Matched MeSH terms: Chemistry, Pharmaceutical
Quantitative analysis of virgin coconut oil in cream cosmetics preparations using fourier transform infrared (FTIR) spectroscopy

Rohman A, Man YC, Sismindari

Pak J Pharm Sci, 2009 Oct;22(4):415-20.
PMID: 19783522

Today, virgin coconut oil (VCO) is becoming valuable oil and is receiving an attractive topic for researchers because of its several biological activities. In cosmetics industry, VCO is excellent material which functions as a skin moisturizer and softener. Therefore, it is important to develop a quantitative analytical method offering a fast and reliable technique. Fourier transform infrared (FTIR) spectroscopy with sample handling technique of attenuated total reflectance (ATR) can be successfully used to analyze VCO quantitatively in cream cosmetic preparations. A multivariate analysis using calibration of partial least square (PLS) model revealed the good relationship between actual value and FTIR-predicted value of VCO with coefficient of determination (R2) of 0.998.

Matched MeSH terms: Chemistry, Pharmaceutical
Fulltext The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling

Hong W, Wang Y, Chang Z, Yang Y, Pu J, Sun T, et al.

Sci Rep, 2015;5:15328.
PMID: 26471125 DOI: 10.1038/srep15328

It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR.

Matched MeSH terms: Chemistry, Pharmaceutical
Formulation and optimization of gastric floating drug delivery system using Central composite design and its biopharmaceutical evaluation

Meka VS, Thing LK, Gorajana A, Kolapalli VR

Pak J Pharm Sci, 2015 Jul;28(4):1373-87.
PMID: 26142528

The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.

Matched MeSH terms: Chemistry, Pharmaceutical
Potential and future scope of nanoemulgel formulation for topical delivery of lipophilic drugs

Sengupta P, Chatterjee B

Int J Pharm, 2017 Jun 30;526(1-2):353-365.
PMID: 28461261 DOI: 10.1016/j.ijpharm.2017.04.068

The Nanoemulgel drug delivery system is a formulation related intervention to improve the systemic delivery and therapeutic profile of lipophilic drugs. Nanoemulgel is an amalgamated formulation of two different systems in which nanoemulsion containing drug is incorporated into a gel base. The fusion of the two systems makes this formulation advantageous in several ways. Lipophilic drugs can be easily incorporated and the skin permeability of the incorporated drugs can be enhanced in several folds due to the finely distributed droplets of nanoemulsion phase. As a result, the pharmacokinetic and pharmacodynamic profiles of the lipophilic drugs are improved significantly. An increasing trend in topical nanoemulgel use in recent years has been noticed because of the better acceptability of the preparation to the patients due to their noninvasive delivery, avoidance of gastrointestinal side effects, easier applicability and good therapeutic and safety profile. Despite of having few limitations, nanoemulgel formulation can be considered as a potential and promising candidates for topical delivery of lipophilic drugs in the future. The aim of this review is to evaluate and report the current potential and future scope of nanoemulgel formulation for becoming an effective delivery system for poorly water soluble drugs. In this review, we have summarized and discussed the outcome of different studies on permeability, pharmacokinetic, pharmacodynamic and safety profile of the drugs delivered topically through nanoemulgel. Rationality of use along with the major challenges to overcome for nanoemulgel formulation has been discussed.

Matched MeSH terms: Chemistry, Pharmaceutical

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