Tujuan kajian ini adalah untuk menilai sifat-sifat fizikokimia Radix Glycyrrhizae sebagai bahan eksipien untuk pembuatan tablet dengan kaedah pemampatan terus dan membandingkannya dengan eksipien komersil iaitu laktosa, selulosa mikrohablur (MCC) dan kalsium laktat pentahidrat (Puracal). Saiz partikel untuk semua sampel yang digunakan dalam kajian ini dihadkan pada 200-250µm. Hasil imbasan elektron mikroskop menunjukkan partikel Radix Glycyrrhizae mempunyai kepelbagaian saiz dan bentuk yang tidak seragam seperti laktosa berbanding MCC yang lebih bersifat jejarum dan Puracal yang bersifat sfera dan poros. Keupayaan sampel untuk dimampatkan, ketumpatan partikel sampel, kesan kelembapan ke atas tegasan pengenduran dan keliangan tablet diuji serta dibandingkan dengan eksipien komersil yang lain. Sifat ikatan dari sampel Radix Glycyrrhizae ini pula dikaji dengan menghitung kekuatan tegangan melalui kaedah pemampatan diametral dan turut dilakukan perbandingan. Radix Rlycyrrhizae memiliki ketumpatan sebenar serbuk iaitu 1.5746 g/cc manakala laktosa, selulosa mikrohablur dan kalsium laktat pentahidrat masing-masing 1.5476, 1.6654 dan 1.3506 g/cc. Radix Rlycyrrhizae juga di dapati mempunyai daya ketermampatan yang sederhana sebagaimana laktosa berbanding Puracal dan MCC yang jauh lebih baik sifatnya. Kajian kesan kelembapan menunjukkan kekuatan tablet Radix Glycyrrhizae, Puracal, laktosa dan MCC dipengaruhi perubahan suhu. Hasil kajian analisis Heckel pula menunjukkan bahawa Radix Glycyrrhizae bersifat aliran plastik sebagaimana MCC manakala laktosa dan Puracal lebih bersifat rapuh. Keputusan ujian ke atas sifat pemampatan dan pemadatan mendapati bahawa Radix Kesimpulannya, Radix Glycyrrhizae boleh digunakan sebagai eksipien dalam pembuatan tablet melalui kaedah pemampatan terus dan ciriciri fisikokimianya sebagai eksipien adalah setanding dengan eksipien komersial.
Polyvinyl chloride (PVC) and ammonio methacrylate copolymer (Eudragit RS 100) were used as models in binary mixture tablets of direct compression study. Eudragit RS 100 is a copolymer synthesized from acrylic and methacrylic acid esters with a low content of quaternary ammonium groups. Combination of PVC and Eudragit RS 100 of different polarities and knowing the surface free energy values allow the possibility of predicting the tensile strength of the tablets. Specimens of 500 mg in the form of thin plates (25 mm x 12.5 mm), were made by compressing each powder at 20 000 MP a compression pressure using a special punch and die set. A Howden Universal Testing Machine was used to compress the powder. Contact angle measurements of the samples were carried out using a Wilhelmy balance, ran by a Cahn Dynamic Contact Angle Machine while different test liquids media such as water, glycerol, formamide and PEG 200 were used in the study. The surface free energy values of the solid materials were calculated using Wu's equation. The results showed large differences between the advancing and receding contact angle values for both materials when tested with glycerol: PVC (0) and PVC (0,) were 93.2 and 65.24 while Eudragit RS 100 (0) and Eudragit RS 100 (0) were 94.56 and 68.18 respectively. The surface free energy values for PVC using PEG 200-glycerol liquid pair were Is: 38.01, ysci: 33.42, ysP: 4.59 and for Eudragit RS 100 using formamide-glycerol liquid pair were ys: 75.03, yd: 51.66, ysP : 23.37, respectively. The results showed harder solid material like Eudragit RS 100 had higher surface free energy compared to elastic material like PVC.
Herbal medicine is usually made using dry powdered herbs in the form of capsule. Capsule form herbal supplement suffers lower shelf life as compared to compact herbal powder in tablet form. In this study, Diabecine™, a blend of herbal medicine traditionally used as herbal supplement for diabetic patients was selected and transformed into a compressed tablet. Direct compression method and minimal usage of excipients were the aims of this study. By using direct compression, the blend of 40% fine powder herbs and 60% of excipients performed the best and fulfill the pharmaceutical standard. The safety data of microbial and heavy metal testing obtained met the safety requirements for herbal supplement category under the National Pharmaceutical Control Bureau of Malaysia. In conclusion, the tablet formulation of Diabecine™ is suitable to be manufactured by using direct compression method. This research implicates the possibility of producing tablets with high dose of herbal powder by direct compression method.
Penggunaan formulasi tablet pelepasan tertahan untuk dadah anti-inflamatori bukan steroid (DAIBS) seperti aspirin berupaya melindungi lapisan perut dari kesan buruk jus asid tubuh. Kajian ini dilakukan untuk menilai keberkesanan formulasi tablet matriks pelepasan tertahan dengan kepelbagaian kepekatan polimer bersama ketoprofen sebagai model. Tablet dibangunkan dengan menggunakan kaedah granulasi basah yang terdiri daripada polimer hidrofilik (hidroksipropil metilselulosa), polimer hidrifobik bersandar pada pH (Eudragit L100-55) dan polimer tak bersandar pada pH (Eudragit R100) sebagai bahan asas pembentukan matriks pada kepekatan 10, 20 dan 30%b/b. Semua formulasi dimampatkan dengan menggunakan mesin pentabletan yang mempunyai penebuk berbentuk cembung bersaiz 10 mm. Tablet yang terhasil diuji daripada segi keseragaman berat, kekerasan, kerapuhan, ketebalan, peratus kandungan dadah dan kajian pelepasan in vitro menggunakan kaedah BP 2007. Hasil menunjukkan kadar pelepasan dadah dikawal oleh jenis dan kepekatan polimer di dalam formulasi matriks. Secara umumnya peningkatan kepekatan kandungan polimer di dalam tablet matriks didapati mengurangkan kadar pelepasan dadah. Perbandingan polimer melalui kepekatan yang sama menggunakan t50%, pula mendapati terdapat perbezaan statistik bermakna (p<0.05) pada kadar pelepasan dadah. Berdasarkan kepada pelepasan dadah dalam kajian in vitro, polimer hidrofobik bersandar pada pH (Eudragit L100-55) menunjukkan profil pelepasan dadah secara tertib sifar yang terbaik berbanding polimer yang lain.
Nata de coco, a dessert originally from the Philippines is produced by fermentation of coconut water with a culture of Acetobacter xylinum, a gram negative bacterium. Acetobacter xylinum metabolizes glucose in coconut juice and converts it into bacterial cellulose that has unique properties including high purity, crystallinity and mechanical strength. Because the main component of nata de coco is bacterial cellulose, nata de coco was purified, extracted and characterized to determine whether pure cellulose could be isolated from it. The FTIR spectra of bacterial cellulose from nata de coco showed distinguish peaks of 3440 cm-1, 2926 cm-1, 1300 cm-1, 1440 cm-1, 1163 cm-1 and 1040 cm-1, which correspond to O-H stretching, C-H stretching, C-H bending, CH2 bending, C-O-C stretching and C-O stretching, respectively, and represent the fingerprints of pure cellulose component. Moreover, the FTIR curve showed a pattern similar to other bacterial cellulose spectra reported by report. Thermal analysis showed a DTG peak at 342°C, which falls in the range of cellulose degradation peaks (330°C - 370°C). On the other hand, the TGA curve showed 1 step of degradation, and this finding confirmed the purity of nata de coco. Bacterial cellulose powder produced from nata de coco was found to be soluble only in cupriethylenediamine, a well known solvent for cellulose; thus, it was confirmed that nata de coco is a good source of bacterial cellulose. The purity of bacterial cellulose produced from nata de coco renders it suitable for research that uses pure cellulose.
In this research, a novel method was performed to obtain hydrogel with superior thermal stability by incorporation
of cellulose nanocrystals (CNC) into gelatin based hydrogel. Glutaraldehyde was used as cross-linker due to its high
chemical reactivity towards NH2
group on gelatin. Different ratio of gelatin/CNC hydrogel was produced in order to study
the effects of CNC towards the swelling behaviour and thermal stability of gelatin based hydrogel. The obtained hydrogel
was subjected to Fourier transform infrared (FTIR) to verify that gelatin had been cross-linked, swelling test with different
pH for swelling behaviour and thermogravimetric analysis (TGA) for thermal stability. The presence of C=N stretching
group in the FTIR spectrum for gelatin/CNC hydrogel indicated that the cross-linking reaction between gelatin monomer
had been successfully carried out. The hydrogel showed impressive pH sensitivity and maximum swelling was obtained
at pH3. The TGA results clearly showed that the incorporation of CNC into gelatin was able to produce hydrogel with
higher thermal stability compare to neat gelatin.
The objective of this study is to synthesize and evaluate acute toxicity of the bacterial cellulose (BC)/acrylamide (Am) hydrogels as noncytotoxic and biocompatible oral drug delivery vehicles. A novel series of solubilized BC/Am hydrogels were synthesized using a microwave irradiation method. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), swelling ratio, porosity, drug release, and in vitro and in vivo biocompatibility experiments. FTIR spectra revealed that the BC crystallinity and gel fraction decreased as the NaOH concentration increased from 2% to 10% w/v, whereas the optical transparency, pH sensitivity, and porosity were enhanced with increasing alkali concentration. Theophylline was used as a model drug for drug loading and release studies. The percentage of drug released was higher at pH 7.4 compared to pH 1.5. In vitro cytotoxicity and hemolytic tests indicated that the BC/Am hydrogel is noncytotoxic and hemocompatible. Results of acute oral toxicity tests on ICR mice suggested that the hydrogels are nontoxic up to 2000 mg/kg when administered orally, as no toxic response or histopathological changes were observed in comparison to control mice. The results of this study demonstrated that the pH-sensitive smart hydrogel makes it a possible safe carrier for oral drug delivery.
Kajian ini telah menilai kesan pelbagai faktor persekitaran terhadap darjah pengembungan hidrogel selulosa bakteria-asid akrilik. Campuran akues selulosa bakteria-asid akrilik (4:1) telah disediakan dan didedahkan dengan irradiasi alur elektron pada 35 kGy dan 50 kGy. Kadar pengembungan di bawah pengaruh pH, suhu dan kekuatan ionik telah dikaji dari 1 hingga 24 jam. Darjah pengembungan hidrogel bergantung kepada dos irradiasi yang diberi: hidrogel yang telah disintesis pada 50 kGy mempunyai darjah pengembungan yang lebih tinggi secara signifikan (p<0.0001) dalam metanol (619%) berbanding air suling (510%) pada suhu bilik selepas 24 jam. Kekuatan ionik persekitaran mempengaruhi dengan peningkatan kepekatan natrium klorida menurunkan darjah pengembungan. Hidrogel juga peka terhadap perubahan pH: pengembungan meningkat dengan peningkatan pH dan nilai optimal dicapai pada pH 7. Selain itu pengembungan juga meningkat dengan peningkatan suhu dari 25°C sehingga 50°C. Kesimpulannya, keupayaan hidrogel selulosa bakteria-asid akrilik dedahan irradiasi elektron bertindak balas terhadap pelbagai rangsangan faktor persekitaran, menjadikan ia satu bahan yang boleh dibangunkan sebagai sistem penyampaian aktif untuk dadah, protein dan hormon.
There has been an increasing interest in the use of natural materials as drug delivery vehicles due to their biodegradability, biocompatibility and ready availability. These properties make bacterial cellulose (BC), from nata de coco, a promising biopolymer for drug delivery applications. The aim of this study was to investigate the film-coating and drug release properties of this biopolymer. Physicochemical, morphological and thermal properties of BC films were studied. Model tablets were film coated with BC, using a spray coating technique, and in vitro drug release studies of these tablets were investigated. It was found that BC exhibited excellent ability to form soft, flexible and foldable films without the addition
of any plasticizer. They were comparable to Aquacoat ECD (with plasticizer) in tensile strength, percentage elongation and elasticity modulus. Differential scanning calorimetry (DSC) BC showed a high Tg value indicating thermally stability of films. These results suggest that BC can be used as novel aqueous film-coating agent with lower cost and better film forming properties than existing film-coating agents.
Previously, studies have demonstrated that topical application of simvastatin can promote wound healing in diabetic mice via augmentation of angiogenesis and lymphangiogenesis. This study aimed to formulate and characterize simvastatin in alginate-based composite film wound dressings. Biopolymers used for composite films were sodium alginate blended with pectin or gelatin. The films were prepared and characterized based on their physical properties, surface morphology, mechanical strength and rheology. Then, in vitro drug releases from the films were investigated and, finally, the cell viability assay was performed to assess the cytotoxicity profile. From the pre-formulation studies, alginate/pectin composite film showed to possess desirable wound dressing properties and superior mechanical properties. The in vitro drug release profile revealed that alginate/pectin film produced a controlled release drug profile, and cell viability assay showed that the film was non-toxic. In summary, alginate/pectin composite film is suitable to be formulated with simvastatin as a potential wound dressing.
Polymer-Fish oil bigel (hydrogel/oleogel colloidal mixture) was developed by using fish oil and natural (sodium alginate) and synthetic (hydroxypropyl methylcellulose) polymer for pharmaceutical purposes. The bigels were closely monitored and thermal, rheological and mechanical properties were compared with the conventional hydrogels for their potential use as an effective transdermal drug delivery vehicle. Stability of the fish oil fatty acids (especially eicosapentanoic acid, EPA and docosahexanoic acid, DHA) was determined by gas chromatography and the drug content (imiquimod) was assessed with liquid chromatography. Furthermore, in vitro permeation study was conducted to determine the capability of the fish oil-bigels as transdermal drug delivery vehicle. The bigels showed pseudoplastic rheological features, with excellent mechanical properties (adhesiveness, peak stress and hardness), which indicated their excellent spreadability for application on the skin. Bigels prepared with mixture of sodium alginate and fish oil (SB1 and SB2), and the bigels prepared with the mixture of hydroxypropyl methylcellulose and fish oil (HB1-HB3) showed high cumulative permeation and drug flux compared to hydrogels. Addition of fish oil proved to be beneficial in increasing the drug permeation and the results were statistically significant (p < 0.05, one-way Anova, SPSS 20.0). Thus, it can be concluded that bigel formulations could be used as an effective topical and transdermal drug delivery vehicle for pharmaceutical purposes.
Bacterial cellulose (BC) is a biopolymer with significant potential for the development of novel materials. This work aimed to prepare and characterize BC powders from nata de coco, and assess the possible enhancement of the powder properties by spray drying. Therefore, BC powders prepared by acid treatment and mechanical processing were spray-dried, and characterized according to their morphology, flowability, thermal stability, water retention capacity, and compared with commercial microcrystalline cellulose (MCC). The powders redispersibility and suspensions rheology were also evaluated. SEM showed that spray-dried BC microparticles exhibited semispherical shape and had flow rate of 4.23 g s(-1) compared with 0.52 g s(-1) for MCC. Particle size analysis demonstrated that spray-dried BC microparticles could be redispersed. TGA showed that BC samples had higher thermal stability than MCC. Water retention capacities of BC samples were greater than MCC. These findings provide new insight on the potential applications of spray-dried BC as a promising pharmaceutical excipient.
Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.
Oral insulin administration suffers gastrointestinal tract (GIT) degradation and inadequate absorption from the intestinal epithelium resulting in poor bioavailability. This study entails in vitro and in vivo assessment of stimuli-responsive hydrogel microparticles (MPs) in an attempt to circumvent GI barrier and enhance oral insulin bioavailability.
Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.
The current conventional injectable vaccines face several drawbacks such as inconvenience and ineffectiveness in mucosal immunization. Therefore, the current development of effective oral vaccines is vital to enable the generation of dual systemic and mucosal immunity. In the present study, we examine the potential of pH-responsive bacterial nanocellulose/polyacrylic acid (BNC/PAA) hydrogel microparticles (MPs) as an oral vaccine carrier. In-vitro entrapment efficiency and release study of Ovalbumin (Ova) demonstrated that as high as 72% of Ova were entrapped in the hydrogel, and the release of loaded Ova was pH-dependent. The released Ova remained structurally conserved as evident by Western blot and circular dichroism. Hydrogel MPs reduced the TEER measurement of HT29MTX/Caco2/Raji B triple co-culture monolayer by reversibly opening the tight junctions (TJs) as shown in the TEM images. The ligated ileal loop assay revealed that hydrogel MPs could facilitate the penetration of FITC-Ova into the Peyer's patches in small intestine. Ova and cholera toxin B (CTB) were utilized in in-vivo oral immunization as model antigen and mucosal adjuvant. The in-vivo immunization revealed mice orally administered with Ova and CTB-loaded hydrogel MPs generated significantly higher level of serum anti-Ova IgG and mucosal anti-Ova IgA in the intestinal washes, compared to intramuscular administrated Ova. These results conclude that BNC/PAA hydrogel MPs is a potential oral vaccine carrier for effective oral immunization.
The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.
Various swelling drug delivery devices are promising materials for control drug delivery because of their ability to swell and release entrapped therapeutics, in response to physiological stimuli. Previously, many mathematical models have been developed to predict the mechanism of drug release from a swelling device. However, some of these models do not consider the changes in diffusion behaviour as the device swells. Therefore, we used a two-phase approach to simplify the mathematical model considering the effect of swelling on the diffusion coefficient. We began by defining a moving boundary problem to consider the swelling process. Landau transformation was used for mitigating the moving boundary problem. The transformed problem was analytically solved using the separation of variables method. Further, the analytical solution was extended to include the drug release in two phases where each phase has distinct diffusion coefficient and continuity condition was applied. The newly developed model was validated by the experimental data of bacterial cellulose hydrogels using the LSQCURVEFIT function in MATLAB. The numerical test showed that the new model exhibited notable improvement in curve fitting, and it was observed that the initial effective diffusion coefficient of the swelling device was lower than the later effective diffusion coefficient.
Natural polymer-based hydrogel films have great potential for biomedical applications and are good candidates for wound dressings. In this study, we aimed to develop simvastatin-loaded crosslinked alginate-pectin hydrogel films by ionic crosslinking to improve the mechanical characteristics, wound fluid uptake and drug release behavior. Alginate-pectin hydrocolloid films were chemically crosslinked by immersing in different concentrations of CaCl2 (0.5-3% w/v) for 2-20min. The degree of crosslinking was influenced by both contact time and CaCl2 concentration. The optimized conditions for crosslinking were 0.5% and 1% (CaCl2) for 2min. The optimized hydrogel films were then characterized for their physical, mechanical, morphological, thermal, in vitro drug release, and cytocompatibility profiles. Crosslinking improved the mechanical profile and wound fluid uptake capacity of dressings. The hydrogel films were able to maintain their physical integrity during use, and the best results were obtained with the film in which the extent of crosslinking was low (0.5%). Thermal analysis confirmed that the crosslinking process enhanced the thermal stability of hydrogel films. Sustained, slow release of simvastatin was obtained from the crosslinked films and in vitro cytotoxicity assay demonstrated that the hydrogel films were non-toxic.