ABSTRACT
PURPOSE: The current work aimed to develop spray-dried silica xerogel nanoparticles (SXNs) as a gastroretentive carrier for the dual delivery of chlorambucil (CHL) and granisetron hydrochloride (GR). As a low-density system, it was proposed to float over gastric fluids; allowing for the retention of CHL in the acidic medium where it is more stable while ensuring the solubility of GR. METHODS: Silica xerogels were developed by sol-gel process, using Tetraethyl orthosilicate (TEOS) water and acetic acid, followed by spray drying. SXNs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), CHL and GR release after 1 hr (P1h) and after 8 hrs (P8h). The best achieved system (SXN4) was evaluated for morphology, pore diameter, total porosity, bulk density, wetting time, floating characteristics. Furthermore, the pharmacokinetics of the loaded drugs were evaluated in rats; relative to an aqueous CHL suspension containing GR. RESULTS: SXN4 system had the highest desirability (0.69); showing spherical nanoparticles (181.63 nm), negative zeta potential (-5.18 mV), promising EE% of 59.39% and 73.94% (for CHL and GR, respectively) and sustained CHL and GR release profiles characterized by low P1h (22.75% and 30.74%) and high P8h (60.36% and 99.33%), respectively. It had a mean pore diameter of 8.622 nm, a total porosity of 62.27%, a bulk density of 0.605 g/mL, a wetting time of 292 sec, zero lag time and a floating duration of at least 8 h. CONCLUSION: The prolongation in the mean residence time (MRT(0-∞)) and the promotion of the relative oral bioavailabilities of both drugs could unravel the potential of this system for the management of chemotherapy-induced nausea and vomiting.
Subject(s)
Antineoplastic Agents/adverse effects , Gels/chemistry , Nanoparticles/chemistry , Nausea/drug therapy , Silicon Dioxide/chemistry , Stomach/drug effects , Vomiting/drug therapy , Animals , Chlorambucil/blood , Chlorambucil/pharmacokinetics , Chlorambucil/pharmacology , Chlorambucil/therapeutic use , Drug Delivery Systems , Drug Liberation , Male , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Nausea/chemically induced , Nausea/pathology , Particle Size , Porosity , Rats , Rats, Wistar , Solubility , Static Electricity , Time Factors , Vomiting/chemically induced , Vomiting/pathologyABSTRACT
The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that Cmax and AUC0-6 h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.
Subject(s)
Adhesives/administration & dosage , Adhesives/chemistry , Brain/drug effects , Gels/chemistry , Granisetron/administration & dosage , Granisetron/chemistry , Nasal Mucosa/metabolism , Administration, Intranasal/methods , Animals , Biological Availability , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation/drug effects , Gels/administration & dosage , Lactose/analogs & derivatives , Lactose/chemistry , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Rats , Rats, WistarABSTRACT
BACKGROUND & OBJECTIVE: Our research objective was to design, develop, optimize and characterize Granisetron HCl transdermal gel in order to minimize side effects associated with oral delivery. METHOD: A statistical design was practically applied for further optimization and preparation of transfersomal gel using Box-Behnken methodology at three levels. The selected independent and dependent variables were Lipoid, surfactant and sonication time and encapsulation efficiency, size and flux correspondingly. RESULT: The optimized formulation (GTV-16) morphology, shape, size, potential, encapsulation capacity and flux (using Franz-diffusion cell assembly via animal skin barricade medium) were determined. Then, GTV-16 incorporated into gel and during evaluation nano-transformal gel has good particle size of 127.7±1.08 nm, better entrapment efficiency of 83.0 ± 3.22 % and flux of 20.0 ± 1.88µgcm-2/h. CONCLUSION: The results demonstrated that Granisetron Hydrochloride loaded nano-gel was significantly superior with 8.5 fold enhancement in bioavailability as compared with drug solution.
Subject(s)
Drug Carriers/chemistry , Granisetron/chemistry , Nanoparticles/chemistry , Administration, Cutaneous , Biological Availability , Chemistry, Pharmaceutical , Deoxycholic Acid/chemistry , Drug Liberation , Excipients/chemistry , Gels , Granisetron/administration & dosage , Humans , Hydrophobic and Hydrophilic Interactions , Lipids/chemistry , Particle Size , Permeability , Polysorbates/chemistry , Skin Absorption , SonicationABSTRACT
Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h. Concentration was measured using high-performance liquid chromatography (HPLC). The appearance and pH of the mixed solutions did not change for up to 24 h. The change in concentration up to 24 h was within 2%. The chromatogram did not change until 8 h. The results showed that the physical compatibility and chemical stability of nab-paclitaxel were not influenced when it was combined with other drugs until 8 h. This study suggests that nab-paclitaxel could be administered in a mixture or sequentially with other drugs to reduce administration time.
Subject(s)
Albumins/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Granisetron/pharmacology , Paclitaxel/pharmacology , Albumins/administration & dosage , Chromatography, High Pressure Liquid/methods , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacology , Drug Combinations , Drug Incompatibility , Drug Stability , Female , Granisetron/administration & dosage , Humans , Infusions, Intravenous , Male , Paclitaxel/administration & dosage , Risk Factors , GemcitabineABSTRACT
The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release proï¬le. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.
Subject(s)
Antiemetics , Drug Delivery Systems/methods , Granisetron , Hypromellose Derivatives , Mouth Floor , Polyvinyls , Administration, Oral , Animals , Antiemetics/chemistry , Antiemetics/pharmacokinetics , Antiemetics/pharmacology , Drug Evaluation, Preclinical , Goats , Granisetron/chemistry , Granisetron/pharmacokinetics , Granisetron/pharmacology , Hypromellose Derivatives/chemistry , Hypromellose Derivatives/pharmacokinetics , Hypromellose Derivatives/pharmacology , Polyvinyls/chemistry , Polyvinyls/pharmacokinetics , Polyvinyls/pharmacologyABSTRACT
Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest compliance of the patients, especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to withstand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. The purpose of this research was to mask the bitter taste of granisetron hydrochloride. To mask the taste Kollicoat(r) Smartseal 30D was used as coating polymer for pellet coating. The coated pellets of the drug was directly compressed with different superdisintegrant as AC-Di-Sol, Explotab and Kollidon CL in different concentration 5.0-7.5% w/w into an ODT. The prepared tablets were evaluated for hardness, friability, weight variation, wetting time, wet absorption ratio, in-vitro disintegration time and in vitro dissolution studies. Tablets exhibited quick disintegration characteristics with Kollidon CL in concentration 7.5% w/w i.e., within 20 seconds, which is characteristic of orally disintegrating dosage forms. More than 98% of drug was released from the formulations within 15 minutes. Formulations subjected to stability testing as per the ICH guidelines for 3 months, indicated stability with no change in taste, hardness, drug content, disintegration time and dissolution profiles. Thus, the results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated dosage forms in the oral cavity.
Sistemas de desintegração oral têm um nicho entre os sistemas de administração de medicamentos por via oral devido à maior aceitação dos pacientes, especialmente os de geriatria e pediatria. Além disso, pacientes que sofrem de disfagia, enjoo de movimento, emese repetida e distúrbios mentais preferem estes medicamentos porque não podem engolir grande quantidade de água. Além disso, os fármacos que exibem absorção satisfatória a partir da mucosa oral ou que se destinam a ação farmacológica imediata podem ser vantajosamente formulados nestas formas de dosagem. No entanto, a formulação destas formas farmacêuticas exige-lhes resistência mecânica suficiente para suportar os rigores do manuseio e capacidade de desintegrar dentro de alguns segundos em contato com a saliva. O objetivo desta pesquisa foi o de mascarar o gosto amargo de cloridrato de granisetrona. Para mascarar o sabor, utilizou-se Kollicoat smartseal 30D como polímero para io revestimento dos péletes. Os péletes revestidos do fármaco foram diretamente comprimidos com superdesintegrante diferente como Ac-Di-Sol, Explotab e Kollidon CL, em diferentes concentrações 5.0-7.5% m/m em comprimidos de dispersão oral (ODT). Os comprimidos preparados foram avaliados quanto à dureza, friabilidade, variação de peso, ao tempo de umedecimento, à razão de absorção de umidade, ao tempo de desintegração in vitro e em estudos de dissolução in vitro. Os comprimidos apresentaram características de desintegração rápida com Kollidon CL, em concentração de 7,5% m/m, ou seja, dentro de 20 segundos, o que é característico para formas farmacêuticas de desintegração oral. Mais do que 98% do fármaco foi liberado a partir das formulações no prazo de 15 minutos. Formulações submetidas a testes de estabilidade de acordo com as diretrizes da ICH por 3 meses indicaram estabilidade sem alteração no sabor, dureza, teor de fármaco, tempo de desintegração e perfis de dissolução. Assim, os resultados demonstraram que o mascaramento de gosto foi bem-sucedido e atingiu-se rápida desintegração das formas de dosagem na cavidade oral.
Subject(s)
Tablets/pharmacokinetics , Chemistry, Pharmaceutical , Granisetron/analysis , Administration, Buccal , Drug Administration RoutesABSTRACT
Granisetron hydrochloride (granisetron) is a potent antiemetic that has been proven to be effective in acute and delayed emesis in cancer chemotherapy. Granisetron suffers from reduced oral bioavailability (≈60%) due to hepatic metabolism. In this study the combined advantage of provesicular carriers and buccal drug delivery has been explored aiming to sustain effect and improve bioavailability of granisetron via development of granisetron provesicular buccoadhesive tablets with suitable quality characteristics (hardness, drug content, in vitro release pattern, exvivo bioadhesion and in vivo bioadhesion behavior). Composition of the reconstituted niosomes from different prepared provesicular carriers regarding type of surfactant used and cholesterol concentration significantly affected both entrapment efficiency (%EE) and vesicle size. Span 80 proniosome-derived niosomes exhibited higher encapsulation efficiency and smaller particle size than those derived from span 20. Also, the effect of %EE and bioadhesive polymer type on in vitro drug release and in vivo performance of buccoadhesive tablets was investigated. Based on achievement of required in vitro release pattern (20-30% at 2h, 40-65% at 6h and 80-95% at 12h), in vivo swelling behavior, and in vivo adhesion time (>14 h) granisetron formulation (F19, 1.4 mg) comprising HPMC:carbopol 974P (7:3) and maltodextrin coated with the vesicular precursors span 80 and cholesterol (9:1) was chosen for in vivo study. In vivo pharmacokinetic study revealed higher bioavailability of buccal formulation relative to conventional oral formulation of granisetron (AUC0-∞ is 89.97 and 38.18 ng h/ml for buccal and oral formulation, respectively). A significantly lower and delayed Cmax (12.09±4.47 ng/ml, at 8h) was observed after buccal application compared to conventional oral tablet (31.66±10.15 ng/ml, at 0.5 h). The prepared provesicular buccoadhesive tablet of granisetron (F19) might help bypass hepatic first-pass metabolism and improve bioavailability of granisetron with the possibility of reducing reported daily dose (2mg) and reducing dosing frequency.
Subject(s)
Antiemetics , Granisetron , Adhesiveness , Administration, Buccal , Adult , Animals , Antiemetics/administration & dosage , Antiemetics/blood , Antiemetics/chemistry , Antiemetics/pharmacokinetics , Biological Availability , Chemistry, Pharmaceutical , Chickens , Cholesterol/chemistry , Granisetron/administration & dosage , Granisetron/blood , Granisetron/chemistry , Granisetron/pharmacokinetics , Hardness , Hexoses/chemistry , Humans , In Vitro Techniques , Male , Mouth Mucosa/chemistry , Mouth Mucosa/metabolism , Polysaccharides/chemistry , Rabbits , TabletsABSTRACT
Objective To observe the efficacy of a rotating magnetic field and granisetron hydrochloride in preventing nausea and vomiting caused by a eisplatin regimen, and any side effects. Methods Sixty-eight patients receiving cisplatin regimen chemotherapy were randomly assigned to two groups: a magnetic treatment group and a drug treatment group. The patients in the two groups were exposed to a rotating magnetic field or received granisetron hydrochloride, respectively. The effects of the treatments were observed. Results Both treatments could effectively prevent and treat the vomiting caused by chemotherapy. The rate of response to the rotating magnetic field was 88.2% and to the drug 91.2%. However, tardive vomiting was significantly better controlled in the rotating magnetic field group. The incidence of side effects in the magnetic field group was 20.6% , and in the drug treatment group it was 45.6%. Conclusion The efficacy of a rotating magnetic field and granisetron in treating acute vomiting were simi- lar. The rotating magnetic field was more effective in preventing tardive vomiting and had fewer side effects. Magnetic therapy should be more generally applied in clinical practice.
ABSTRACT
OBJECTIVE:To prepare granisetron hydrochloride nasal spray and establish a method for its quality control. METHODS: Granisetron hydrochloride nasal spray was prepared using granisetron hydrochloride as chief ingredient and its content was determined by UV spectrophotometry. RESULTS: Spray appeared as colorless or yellowish supernatant liquid and it was up to the standard specified in Chinese Pharmacopeia (2005 edition). The linear range of granisetron hydrochloride was 105.9～635.4 ?g?mL-1 (r=0.999) and its average recovery rate was 100.1% (RSD=0.4%). CONCLUSION: The preparation is simple and feasible in preparation process and its quality is controllable.
ABSTRACT
Objective To study the effects of granisetron hydrochloride on vasovagal syncope(VVS) in rabbits.Methods Twenty-four healthy New Zealand rabbits were divided stochastically into control group and intervention group,12 in each group. The control group was injected intravenously with normal saline. The intervention group was injected intravenously with granisetron hydrchloiride.Rabbit VVS models were established,each was taken at 4 points in time in the bloodletting process:T1,T2,T3,T4,to compare the bloodletting time,the concentration of 5-hydroxytryptamine(5-HT) in T2,T3,T4 and the total blood volume between the groups,and monitor the heart rate, blood pressure during the entire process.Results 1.The time of intervention group in T2,T3,T4 was longer than the time of control group obviously(P
ABSTRACT
OBJECTIVE:To study the therapeutic effect of granisetron on postoperative nausea and vomiting(PONV) under patient controlled analgesia(PCA) and to observe the influence of infusion rate of granisetron on blood circulation during operation METHODS: 90 selective surgical patients were divided into 3 groups A group(control):ondonsetron 8mg;B group:tropiestron 3mg; C group:granisetron 3mg The solutions of granisetron hydrochloride were infusied at 20,30,40,50 and 60 min before the end of operation The change of the circulation condition and the status of nausea and vomiting were observed at infusion period and 4,8,12,24hs,2d and 3d postoperatively RESULTS:Under expansion of blood volume,if infusion duration was longer than 20 min for granisetron,the circulation condition(MAP,HR) were not affected during infusion period and no headache was found There were significant differences in PONV between group A and group B(P
