Nasal administration of metoclopramide from different dosage forms: in vitro,ex vivo,and in vivo evaluation

Nasal drug delivery is an interesting route of administration for metoclopramide hydrochloride (MTC) in preventing different kind of emesis. Currently, the routes of administration of antiemetics are oral or intravenous, although patient compliance is often impaired by the difficulties associated with acute emesis or invasiveness of parenteral administration. In this perspective, nasal dosage forms (solution, gel, and lyophilized powder) of MTC were prepared by using a mucoadhesive polymer sodium carboxymethylcellulose (NaCMC). In vitro and ex vivo drug release studies were performed in a modified horizontal diffusion chamber with cellulose membrane and excised cattle nasal mucosa as diffusion barriers. The tolerance of nasal mucosa to the formulation and its components were investigated using light microscopy. In vivo studies were carried out for the optimized formulations in sheep and the pharmacokinetics parameters were compared with oral solution and IV dosage form. The release of MTC from solution and powder formulations was found to be higher than gel formulation (p?<?0.05). Histopathological examination did not detect any severe damage. Hydroxypropyl-β-cyclodextrin (HPβCD) used in powder formulations was found to be effective for enhancing the release and absorption of MTC. In contrast to in vitro and ex vivo experiments nasal bioavailability of gel is higher than those of solution and powder (p?<?0.05). In conclusion, the NaCMC gel formulation of MTC with mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.     

Effect of ion pairing on in vitro transcorneal permeability of a Δ(9) -tetrahydrocannabinol prodrug: potential in glaucoma therapy

The aim of the present study was to evaluate and improve the in vitro transcorneal permeability characteristics of Δ(9) -tetrahydrocannabinol (THC) through prodrug derivatization and formulation approaches. In vitro corneal permeability of THC and its hemisuccinate (THC-HS) and hemiglutarate (THC-HG) ester prodrugs and WIN 55-212-2 (WIN), a synthetic cannabinoid, was determined using isolated rabbit cornea. The formulations studied included hydroxypropyl beta cyclodextrin (HPβCD) or randomly methylated beta cyclodextrin (RMβCD), as well as prodrug-ion-pair complexes with l-arginine or tromethamine. Corneal permeability of WIN was found to be two-fold higher than THC in the presence of HPβCD. THC-HS and THC-HG exhibited pH-dependent permeability. In the presence of HPβCD, at pH 5 (donor solution pH), both prodrugs exhibited six-fold higher permeability compared with THC. However, permeability of the prodrugs was about three-fold lower than that of THC at pH 7.4. RMβCD, at pH 7.4, led to a significant improvement in permeability. Formation of ion-pair complexes markedly improved the solubility and permeability of THC-HG (sevenfold and threefold greater permeability compared with THC and WIN, respectively) at pH 7.4. The in vitro results demonstrate that the use of an ion-pair complex of THC-HG could be an effective strategy for topical delivery of THC.     

A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-β-cyclodextrin (HPβCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPβCD. After pH adjustment, the itraconazole/HPβCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPβCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.     

Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization

The objective of the present research was two-fold: To characterize the produced inclusion complex of felodipine (FDP)-hydroxypropyl-β-cyclodextrin (HPβCD) utilizing lyophilization, and to develop and characterize a complexed sustained-release polymeric matrix tablets intended for buccal delivery. The phase-solubility diagram suggested an A(L) type system with 1:1 stoichiometry. Solid complexes prepared by physical mixing and lyophilization were characterized by thermal and non-thermal analytical techniques to corroborate the fact of complex formation. The sustained-release FDP tablets were produced by direct compression, and these drug or complex-loaded hydrophilic matrices were assessed for in vitro bioadhesion and release modulation, ex vivo permeation, and in vivo residence time. The in vitro drug release and ex vivo permeation across the porcine buccal membrane demonstrated that the matrix tablets containing FDP-HPβCD (FH5) solid complex exhibited a complete and sustained drug release pattern, and a significantly higher drug permeation (p?相似文献   

Development of kit formulations for 99mTcN‐MPO: a cationic radiotracer for myocardial perfusion imaging

The objective of this study was to develop a kit formulation for [^99mTcN(mpo)(PNP5)]⁺ (MPO = 2‐mercaptopyridine oxide), (^99mTcN‐MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two‐vial formulation and single‐vial formulations with/without SnCl₂) to explore the factors influencing radiochemical purity (RCP) of ^99mTcN‐MPO. We found that the most important factor affecting the RCP of ^99mTcN‐MPO was the purity of PNP5. ^99mTcN‐MPO was prepared >98% RCP (n = 20) using the two‐vial formulation. For single‐vial formulations with/without SnCl₂, β‐cyclodextrin (β‐CD) is particularly useful as a stabilizer for PNP5. The RCP of ^99mTcN‐MPO was 95–98% using β‐CD, but its RCP was only 90–93% with γ‐cyclodextrin (γ‐CD). It seems that PNP5 fits better into the inner cavity of β‐CD, which forms more stable inclusion complex than γ‐CD in the single‐vial formulations. The results from biodistribution and imaging studies in Sprague–Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon‐emission computed tomography data suggested that high quality images could be obtained at 0–30‐min post‐injection without significant interference from the liver radioactivity. Considering the ease for ^99mTc‐labeling and high RCP of ^99mTcN‐MPO, the non‐SnCl₂ single‐vial formulation is an attractive choice for future clinical studies.     

Investigation of different emulsion systems for dermal delivery of nicotinamide

Nicotinamide (NA) has been shown to have beneficial effects on several skin diseases such as tumor, acne vulgaris, photodamage, cellulite and atopic dermatitis. The purpose of this study was to develop a multiple emulsion and a microemulsion formulation as delivery systems for NA. A two-step process was used to prepare the W/O/W multiple emulsion. Optimum microemulsion formulation was selected by using construction of pseudo-ternary phase diagram. The physicochemical properties such as droplet size and viscosity measurements, stability studies were also evaluated. Ex-vivo permeation studies were performed with Franz-type diffusion cells and the samples were analysed by high performance liquid chromatography (HPLC). The permeation data showed that there was no significant difference between multiple emulsion and microemulsion (p > 0.05). Transepidermal water loss (TEWL) was also measured. As a result of TEWL studies, a slight increase of TEWL values was observed for microemulsion formulation on rat skin when compared with multiple emulsion and commercial formulation. The results suggested that microemulsion and multiple emulsion formulations could be new and alternative dosage forms for topical application of NA.     

长春西汀微乳的优化及其理化性质的考察

目的选择适宜比例的油相、表面活性剂、助表面活性剂和水相制备长春西汀微乳制剂以增加药物的溶解度和经皮渗透量，优化处方，并对其理化性质和刺激性进行研究。方法绘制伪三元相图，确定各相的比例，以经皮稳态渗透流量为指标，利用单纯形网格法优化处方，并考察优化微乳的pH、粘度、电导率、折光率、粒径分布等理化性质。采用MTT法考察微乳制剂对人体皮肤细胞系模型Hacat细胞的毒性。结果O/W微乳在相图中的区域随着表面活性剂和助表面活性剂比例的增加而增加；单纯形网格优化法预测的指标值与实测值相近，所得的优化微乳性质稳定，对Hacat细胞无刺激性，与阴性组无显著性差异。结论长春西汀微乳制剂中药物的溶解度极大提高，经皮稳态渗透流量显著增大，安全稳定，可作为经皮给药的新型载体。     

Preparation and Characterization of Oxybenzone-Loaded Gelatin Microspheres for Enhancement of Sunscreening Efficacy

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C₅ containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent–loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.     

Entrapment of multiple anti‐Tb drugs in microemulsion system: Quantitative analysis,stability, and in vitro release studies

The use of multiple drug regimes for the treatment of tuberculosis is restricted because of the degradation of Rifampicin in the presence of Isoniazid. In the present report, the microemulsion comprising Tween 80/ethanol/oleic acid/Buffer (pH 7.4) has been investigated for encapsulating Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA) in different combinations. The main idea is to use the compartment of different domains of microemulsion for encapsulating drugs of different solubilties. The structural changes in the microstructure of microemulsion have been investigated in the light of the changes occurring in the presence of ATDs (anti‐Tb drugs) in binary or ternary mixtures through conductivity and viscosity. Optical microscopy and ¹H NMR helped in estimating the shape and location of ATDs in microemulsion system. Electronic spectroscopy has been utilized qualitatively and quantitatively for understanding the stability and release of RIF from the composed formulation with various binary or ternary mixtures. Dissolution and release kinetics have been carried out to get an idea on the release of drugs from microemulsion formulation. ATDs in single and mixed drug formulations followed non‐Fickian release behavior except for RIF in pH 7.4 release medium. The investigations employed have given us a fair success to predict not only the stability but also the release mechanism of ATDs in single and mixed drug formulations. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1896–1911, 2010     

Development of eye drops containing antihypertensive drugs: formulation of aqueous irbesartan/γCD eye drops

Abstract

Aqueous nanoparticulated eye drop formulations based on γ-cyclodextrin (γCD) complexes were developed and tested in vitro. Three antihypertensive drugs, i.e. enalapril maleate, irbesartan and verapamil HCl, that have been shown to possess IOP-lowering activity were selected for this study. All three drugs displayed B_s-type phase-solubility diagrams in aqueous γCD solutions and had relatively low affinity for γCD. Irbesartan was selected for further formulation development. The drug was relatively stable at pH 4.5 but somewhat less stable at physiologic pH. However, presence of γCD in the aqueous media enhanced the chemical stability of irbesartan. Aqueous γCD-based eye drop formulations containing 1% and 2% (w/v) irbesartan were prepared and the effect of pH on the particles size distribution and drug release investigated. Only ～2% of the drug was in solution in the pH 4.5 formulations but up to 45% in the pH 7 formulations. The pH 7 formulations, where larger fraction of the drug was in solution, displayed somewhat greater drug permeation flux but much lower drug permeation coefficients than the pH 4.5 formulations. Dynamic light scattering studies indicated the faster permeation was due to formation of smaller particles in presence tyloxapol.     

In Vitro Tools for Evaluating Novel Dosage Forms of Poorly Soluble,Weakly Basic Drugs: Case Example Ketoconazole

The aim of the present series of experiments was to compare various in vitro tools including evaluation of formulations influence on solubility, various dissolution tests, and an updated, miniaturized transfer model to forecast the behavior of novel formulations of the poorly soluble, weakly basic model compound ketoconazole (KETO) after oral administration. A binary complex with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) and a ternary formulation with HP‐β‐CD and Soluplus® were evaluated and their solubility, dissolution, and transfer behavior was compared with that of the pure drug. Binary and ternary formulations could significantly improve (p < 0.05) KETO solubility in all test media. Dissolution in media simulating the fasted stomach and the fed small intestine was almost complete for the pure drug and both complex formulations. By contrast, in pH 6.5 FaSSIF, dissolution of the pure drug was less than 10%. Both formulations resulted in significantly higher KETO release (p < 0.05) in this test medium (32%/95% release from the binary/ternary formulation). In the transfer experiments, the ternary complex showed the best performance with respect to stabilizing a supersaturated solution and inhibiting precipitation of KETO. Overall, the miniaturized transfer model appeared to be the best single tool for rank‐ordering formulations.     

Development of Mucoadhesive Films for Buccal Administration of Flufenamic Acid: Effect of Cyclodextrin Complexation

A new mucoadhesive film for topical administration in the oral cavity of flufenamic acid, a poorly soluble anti-inflammatory drug, has been developed, using complexation with hydroxypropyl-β-cyclodextrin (HPβCD) to improve drug dissolution and release rate. Buccal films were prepared utilising chitosan as mucoadhesive polymer, KollicoatIR® as film-forming polymer and glycerol as plasticiser. Different combinations of these components were used and the obtained films were characterised for weight, thickness, swelling, mucoadhesive and mechanical properties. The film containing chitosan 2%, glycerol 7.5% and KollicoatIR® 1% showed the best properties for the development of the film formulation. The selected film was loaded with the plain drug and its colyophilised and coground products with HPβCD, and in vitro release studies in simulated saliva were performed. The improved drug dissolution properties, obtained by complexation with HPβCD, were critical to achieve complete release from film formulation during 4–5 h. On the contrary, film loaded with the plain drug showed incomplete release, not exceeding 70% release after 5 h. The developed film formulation containing the drug as complex with HPβCD can assure a prolonged drug release directly at the inflammation site and can be proposed as a new therapeutic tool in the treatment of oral mucosa inflammations.     

Inhibition of Agitation‐Induced Aggregation of an IgG‐Antibody by Hydroxypropyl‐β‐Cyclodextrin

In order to provide an alternative to nonionic surfactants as excipients for protein formulations, cyclodextrin‐derivatives (CDs) were examined for their potential to inhibit agitation‐induced aggregation of an IgG in aqueous solution. Loss of monomeric protein and protein aggregation were monitored throughout the agitation experiments by size exclusion chromatography. Hydroxypropyl‐β‐cyclodextrin (HPβCD) completely suppressed IgG‐aggregation at a remarkably low concentration (2.5 mM) and in contrast to other CDs it also did not negatively affect IgG‐stability during storage in nonagitated solution. Further agitation experiments demonstrated the superiority of HPβCD to other common excipients in protein formulation, such as sugars and sugar alcohols or polysorbate 80 in low concentrations. Spectroscopic (fluorescence spectroscopy and Fourier transform infrared spectroscopy), thermodynamic (microcalorimetry), and physical investigations (surface tension measurements) were carried out to elucidate the mechanism of stabilization of the IgG. In contrast to other studies with HPβCD, protein stabilization could not be attributed to direct interaction between hydrophobic amino acids on the IgG and this excipient. Competition with the protein for the air–water interface appears to be the dominating mechanism of stabilization. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1193–1206, 2010     

Interaction of [d-Trp6, Des-Gly10] LHRH Ethylamide and Hydroxy Propyl β-Cyclodextrin (HPβCD): Thermodynamics of Interaction and Protection from Degradation by α-Chymotrypsin

Purpose: The purpose of this study is to investigate the mechanisms and thermodynamics of the interaction between hydroxypropyl β-cyclodextrin (HPβCD) and [d-Trp ⁶, des-Gly ¹⁰] LHRH ethylamide (deslorelin), a peptide drug. Methods: We used UV and Fluorescence spectroscopy to study the interaction of HPβCD and deslorelin. Circular dichroism was used to study the conformational changes induced in deslorelin upon interaction with HPβCD. The thermodynamics of the interaction of deslorelin and HPβCD was studied using isothermal titration calorimetry (ITC). We also determined the effect of HPβCD on the degradation of deslorelin by α-chymotrypsin. Results: UV and fluorescence spectroscopy indicated that HPβCD induced a change in polarity of the environment surrounding the chromophores of deslorelin. Wavelength selective fluorescence indicated an increase in the fluorescence polarization of deslorelin with an increase in excitation wavelength in the presence of HPβCD suggesting that tryptophan is present in a media of reduced mobility. Circular dichroism studies indicated that HPβCD stabilizes the conformation of deslorelin. In addition, ITC indicated an exothermic reaction between deslorelin and HPβCD with a low enthalpy of binding of ～?600 cal/mol and a binding affinity of ～1.25 × 10 ² M^{? 1}. Finally, the rate of degradation of deslorelin by α-chymotrypsin was decreased by 33% in the presence of HPβCD. Conclusions: These results indicate that there is an interaction between HPβCD and deslorelin, which involves the inclusion of aromatic amino acids of deslorelin into the hydrophobic cavity of the cyclodextrin. This inclusion, providing steric hindrance, may be one of the mechanisms by which HPβCD reduces enzymatic hydrolysis of deslorelin.     

Short term study of human skin irritation by single application closed patch test: assessment of four multiple emulsion formulations loaded with botanical extracts

Background: Assessment of skin irritation potential is a major concern in safety assessment of cosmetics, when long-term use of these products are expected. Non-invasive bioengineering probes have been used previously to measure skin irritation potential of cosmetic ingredients.

Objectives: Experimentation carried out to weigh up the skin irritation potential of four multiple emulsion formulations via visual and non-invasive measurements. Immediate effects of formulations and comparison of two assessment techniques were also tried to establish.

Methods: Four multiple emulsion formulations one control (without botanical active) and three containing the functional botanical actives plus additives were tested in this study using the following techniques: transepidermal water loss (TEWL), COLIPA visual scoring method (CVSM), Mexameter MPA 5 (Courage + Khazaka, Germany) and capacitance [Corneometer MPA 5 (Courage + Khazaka, Germany)]. Visual examination and non-invasive measurements were performed at baseline and after 24?h. The formulations were applied on the forearm of 12 healthy volunteers of same sexes aged 20–25 years.

Results: We found that none of the formulation produced irritation both on visual and instrumental evaluation. However, formulations MeB and MeC have comparable immediate effects on dryness, erythema, melanin and TEWL. Formulation MeC produced more effective results on different parameters, may be due to synergistic effect of two extracts, while MeA failed to produce any immediate effects on skin parameters. Moreover results of both assessment methods are parallel to each other.

Conclusions: None of the formulation produce irritant effects, barrier impairment effects or immediate effects except for the formulation MeC which produced appreciable results than other formulations but statistically these results were insignificant (p?>?0.05). Based on these results, it could be concluded that formulations may be implied safely as skin rejuvenating candidates.     

Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations

To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220?nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA–HPβCD systems showed an A_L type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24?h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6?h incubation period, the cellular uptake was found at 33% and 32% for P–CsA and P–HPβCD–CsA nanoparticles, respectively.     

Non-inclusion complexes between riboflavin and cyclodextrins

Objectives To investigate the molecular interaction between β‐cyclodextrin (βCD) or hydroxypropyl‐β‐cyclodextrin (HPβCD) and riboflavin (RF), and to test the anticancer potential of these formulations. Methods The physicochemical characterization of the association between RF and CDs was performed by UV‐vis absorption, fluorescence, differential scanning calorimetry and NMR techniques. Molecular dynamics simulation was used to shed light on the mechanism of interaction of RF and CDs. Additionally, in‐vitro cell culture tests were performed to evaluate the cytotoxicity of the RF–CD complexes against prostate cancer cells. Key findings Neither βCD nor HPβCD led to substantial changes in the physicochemical properties of RF (with the exception of solubility). Additionally, rotating frame Overhauser effect spectroscopy experiments detected no spatial correlations between hydrogens from the internal cavity of CDs and RF, while molecular dynamics simulations revealed ‘out‐of‐ring’ RF–CD interactions. Notwithstanding, both RF–βCD and RF–HPβCD complexes were cytotoxic to PC3 prostate cancer cells. Conclusions The interaction between RF and either βCD or HPβCD, at low concentrations, seems to be made through hydrogen bonding between the flavonoid and the external rim of both CDs. Regardless of the mechanism of complexation, our findings indicate that RF–CD complexes significantly increase RF solubility and potentiate its antitumour effect.     

In vitro permeation of diclofenac sodium from novel microemulsion formulations through rabbit skin

In order to increase topical penetration of the nonsteroidal anti‐inflammatory drug, diclofenac sodium, new microemulsion formulations were prepared to increase drug solubility and in vitro penetration of the drug. The influence of dimethyl sulfoxide and propylene glycol were also investigated as enhancers on the in vitro penetration of diclofenac sodium using Franz diffusion cells using excised dorsal rabbit skin. Factorial randomized design was performed to analyze the results of in vitro permeation studies. Microemulsions prepared with isopropyl alcohol were superior to those prepared with propanol. Enhancers had different effects depending on the formulation. Propylene glycol was superior to dimethyl sulfoxide when incorporated into isopropyl alcohol microemulsion, whereas dimethyl sulfoxide was superior to propylene glycol in propanol microemulsions. There were no observable histopathological differences between the skin of the control group and the treated groups at the light microscope level due to swelling of the skin tissue. The present study shows that microemulsion formulations containing isopropyl alcohol as co‐surfactant and propylene glycol as enhancer represent a promising approach for a topical vehicle for diclofenac sodium. Drug Dev. Res. 65:17–25, 2005. © 2005 Wiley‐Liss, Inc.     

Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C₅ containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.